Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance. METHODS: The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power. RESULTS: We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity. CONCLUSIONS: These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.

Surface-Plasmonic-Field-Induced Photoredox Catalysis and Mediated Electron Transfer for Washing-Free DNA Detection.

Distance-dependent electromagnetic radiation and electron transfer have been commonly employed in washing-free fluorescence and electrochemical bioassays, respectively. In this study, we combined the two distance-dependent phenomena for sensitive washing-free DNA detection. A distance-dependent surface plasmonic field induces rapid photoredox catalysis of surface-bound catalytic labels, and distance-dependent mediated electron transfer allows for rapid electron transfer from the surface-bound labels to the electrode. An optimal system consists of a chemically reversible acceptor (Ru(NH3 )63+ ), a chemically reversible photoredox catalyst (eosin Y), and a chemically irreversible donor (triethanolamine). Side reactions with O2 do not significantly decrease the efficiency of photoredox catalysis. Energy transfer quenching between the electrode and the label can be lowered by increasing the distance between them. Washing-free DNA detection had a detection limit of approximately 0.3 nm in buffer and 0.4 nm in serum without a washing step.

Occurrence and removal of selected pharmaceuticals and personal care products in three wastewater-treatment plants.

Residues of pharmaceuticals and personal care products (PPCPs) have been detected in surface waters. Incomplete removal of these compounds by wastewater-treatment plants (WWTPs) results in their presence in effluents and finally in surface waters. The occurrence and removal of four PPCPs was investigated in three WWTPs in Mississippi, USA, during a period of 1 year. Influent and effluent were sampled from the three WWTPs. Upstream and downstream samples of the WWTPs were also collected. All four PPCPs were detected in all influents where sulfamethoxazole showed the highest concentration levels with a median concentration of 1,640 ng/L, and carbamazepine was detected at the lowest level with a median concentration of 132 ng/L. Different PPCPs were removed to different extents varying from 99 to 100 %. Gemfibrozil showed the highest removal rates (73-100 %), whereas carbamazepine showed the lowest (-99 to -30 %). Secondary activated sludge in oxidation-ditch process showed remarkable PPCP-specific removal rates. Galaxolide was removed more than the other PPCPs, and sulfamethoxazole showed the least removal. Galaxolide was found to be a predominant PPCP in effluent among the PPCPs studied, and it was detected in all downstream (14.1-428.2 ng/L) and upstream (4.1-60.0 ng/L) samples. Sulfamethoxazole was removed more during the summer than the winter season. A clear increase of PPCP concentrations was observed in most downstream samples compared with upstream samples suggesting that discharges from WWTPs are the major source of PPCPs in surface waters.

Analysis of estrogens in wastewater using solid-phase extraction, QuEChERS cleanup, and liquid chromatography/ tandem mass spectrometry.

We present an improved method for trace level quantification of five estrogens including estriol, estrone, 17alpha-estradiol, 17beta-estradiol, and 17alpha-ethinylestradiol in wastewaters. Our method includes sample preparation using SPE followed by a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) cleanup step, a derivatization, and LC/MS/MS determination. Sample extraction was carried out using Oasis HLB cartridges and a dispersive solid-phase cleanup pack containing MgSO4 and primary-secondary amine and C18 sorbents. The resulting extract was derivatized with dansyl chloride. Separation was achieved on an Agilent Zorbax Extend C18, Narrow Bore RR 2.1 x 100 mm, 3.5 pm column; quantification was accomplished in the positive ion mode using multiple reaction monitoring. The cleanup method is quick, efficient, inexpensive, and requires only 200 mL of water. Reliable linearities were obtained for all calibration curves (r2 > 0.995). Matrix effects calculated were less than 12% for all analytes, and, hence, matrix matched calibration curves were not needed. The recoveries for the estrogens ranged from 81-103%, with a high repeatability (n = 3, RSD < or = 9%) and low LOQs (0.6-0.9 ng/L). The method was used to analyze effluent and influent wastewaters in Mississippi wastewater treatment plants, but it is broadly applicable for the determination of trace estrogens in any municipal wastewater samples.

Transformation of triclosan and triclocarban in soils and biosolids-applied soils.

Triclosan (TCS) and triclocarban (TCC), widely used as antibacterial agents, have been frequently detected in biosolids. Biosolids land application may introduce pharmaceuticals and personal care products (PPCPs) such as TCS and TCC into the environment. Microcosm studies were conducted to investigate TCS and TCC transformation in Marietta fine loam and McLaurin coarse loam. Both compounds were spiked into the soils with and without biosolids amendment under non-sterilized and sterilized conditions and incubated aerobically at 30 degrees C for up to 100 d. In both soils, transformation of TCS followed second-order reaction kinetics, with estimated reaction rate constants of (5.27 +/- 0.920) x 10(-1) and (9.13 +/- 1.58) x 10(-2) (mg kg(-1))(-1) d(-1) for Marietta fine loam and McLaurin coarse loam, respectively. Transformation of TCC in both soils was slower than that for TCS. After 100 d, 53 +/- 1% and 71 +/- 2% of the initially added TCC and only 2.8 +/- 0.35% and 6.2 +/- 0.80% of initially added TCS remained in Marietta fine loam and McLaurin coarse loam, respectively. The transformation of both compounds were faster in the Marietta fine loam (pH 7.8; 1.8% organic matter) than in the McLaurin coarse loam (pH 4.7; 0.65% organic matter). Our result suggests that biotic processes are more of a controlling factor affecting TCS transformation, whereas abiotic processes may affect TCC transformation more significantly. Addition of biosolids to the two soils slowed the transformation of both compounds, indicating interactions between both compounds and biosolids may adversely affect their transformation in soils, an important factor that must be included in models predicting environmental fate of biosolids-associated PPCPs.

Assessment of the toxicological interaction of sertraline with cholinesterase inhibiting insecticides in aquatic insects using the black fly, Simulium vittatum IS-7.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) prescribed as an antidepressant. Although SSRIs are known to block serotonin reuptake sites on cell membranes, they also have been shown to inhibit acetylcholinesterase (AChE) activity. Thus, the interaction of these chemicals with other AChE inhibitors, namely, organophosphate and carbamate insecticides, is of interest. In addition, these insecticides have been shown to interact with serotonergic neuronal pathways creating questions as to how these chemicals might interact. In this study, the interactive effect of sertraline (SSRI) in binary combinations with carbaryl (carbamate insecticide) and diazinon (organophosphate insecticide) was assessed using a 48-h acute toxicity test with black fly larvae, Simulium vittatum IS-7. Results showed that observed mortality was bracketed by the independent action model and concentration addition model with the independent action model slightly underestimating mortality and the concentration addition model slightly overestimating mortality. Varying the concentration of the chemicals in the mixture did not indicate that sertraline was interacting with the insecticides to make them more toxic or vice versa. These results indicate that sertraline and the insecticides are likely eliciting toxicity at separate neuronal pathways since no interaction was observed.

Growth and development of tadpoles (Xenopus laevis) exposed to selective serotonin reuptake inhibitors, fluoxetine and sertraline, throughout metamorphosis.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed drugs that are present in sewage effluents and surface waters. The objective of the present study was to determine whether low environmentally relevant concentrations of the SSRIs fluoxetine and sertraline could impair growth and development in tadpoles of the African clawed frog (Xenopus laevis) and to evaluate if such effects may be caused by a disruption of the neuroendocrine system. Tadpoles were exposed to SSRIs at concentrations of 0.1, 1, and 10 microg/L for 70 d throughout metamorphosis. No effects on deformities were observed. Tadpoles exposed to fluoxetine (10 microg/L) and sertraline (0.1, 1, and 10 microg/L) exhibited reduced growth at metamorphosis. Tadpoles exposed to sertraline (0.1 and 1 microg/L) exhibited an acceleration of development as indicated by an increase in the time to tail resorption. The effects of SSRIs on growth and development in tadpoles were likely driven by reduced food intake. Reduced feeding rates were observed in SSRI-exposed tadpoles, and nutritional status can influence growth and development in amphibians via effects on the neuroendocrine system. Only sertraline was capable of causing developmental toxicity in tadpoles at environmentally relevant concentrations. These data warrant additional research to characterize the risks to human health and wildlife from pharmaceutical exposures.

Determination of 17alpha-ethynylestradiol, carbamazepine, diazepam, simvastatin, and oxybenzone in fish livers.

A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed for the determination of 17alpha-ethynylestradiol in fish liver; a second method using LC/MS was developed for the determination of carbamazepine, diazepam, simvastatin, and oxybenzone in fish liver. The fish liver samples were extracted and cleaned up by using liquid-liquid extraction and solid-phase extraction before the extracts were analyzed by LC/MS or LC/MS/MS with electrospray negative and positive ionization. Recoveries of the 5 target compounds from spiked catfish liver ranged from 72 +/- 2 to 100 +/- 3%. Limits of quantification for the 5 compounds were between 4.2 and 12.3 ng/g (wet weight). Ten turbot (Pleuronichthys verticalis) liver samples were analyzed; levels of 17alpha-ethynylestradiol, carbamazepine, simvastatin, and oxybenzone were below the detection limits. Diazepam was detected in all 10 fish liver samples at concentrations ranging from 23 to 110 ng/g (wet weight).

Degradation of chlorothalonil in irradiated water/sediment systems.

Water/sediment systems were used to investigate partitioning behavior between waters and sediments, as well as the degradation of the fungicide chlorothalonil (CHT) in each matrix. Experiments were run in the light and dark simultaneously for 30 days in both creek and pond sediment systems. Of the total applied CHT, 87-88% dissipated from the water phase in both water/sediment systems within 1 day when irradiated by simulated sunlight. In contrast, 60-68% remained in the water at day 1 in the dark. Approximately 3-6 and 10-16% of the applied CHT was found in sediments under light conditions at day 1 and in the dark at day 3, respectively which are the highest amounts observed during the experimental period. CHT similarly behaved in irradiated water/sediments and sediment-free aqueous solutions, indicating that CHT primarily degraded by photodegradation rather than adsorption to sediment in the early stages of the experiment. 4-Hydroxychlorothalonil was detected only in water in the dark systems. Trichloro-1,3-dicyanobenzene and 3-cyano-2,4,5,6-tetrachlorobenzamide were also detected and identified with liquid chromatography-electrospray ionization-mass spectrometry. These results suggest that photodegradation is likely to be important to the dissipation of CHT in aqueous solutions and microbial degradation plays an important role for residues that would ultimately reside in sediment.

Laboratory persistence and fate of fluoxetine in aquatic environments.

The persistence and fate of fluoxetine, a selective serotonin reuptake inhibitor, has been investigated in laboratory-scale experiments, including studies with various aqueous solutions, water/sediment systems, and activated sludge-amended medium. The samples were placed in the dark and/or in a growth chamber fitted with fluorescent lamps simulating the ultraviolet output of sunlight. Over a period of 30 d, fluoxetine was hydrolytically and photolytically stable in all aqueous solutions except synthetic humic water (pH 7), in which the degradation rate was increased by approximately 13-fold in comparison with buffered solutions at the same pH. Fluoxetine rapidly dissipated from the aqueous phase in water/sediment systems, primarily because of distribution to sediments. The dissipation rate from the aqueous phase was similar between light and dark systems, indicating a low contribution of photodegradation to the dissipation of fluoxetine in this system. The potential impact of fluoxetine in aquatic environments would be decreased because of adsorption to sediments. Based on results of ready-biodegradability investigations, fluoxetine would not be expected to rapidly biodegrade in wastewater treatment plants. A photoproduct was detected only in a sample of synthetic humic water and was identified as norfluoxetine formed by demethylation. Results indicate that fluoxetine is relatively recalcitrant to hydrolysis, photolysis, and microbial degradation and that it is rapidly removed from surface waters by adsorption to sediment, where it appears to be persistent.

Photo-isomerization of fluvoxamine in aqueous solutions.

The hydrolysis and photolysis of fluvoxamine, a selective serotonin reuptake inhibitor, in aqueous buffer solutions (pH 5, 7, and 9), in synthetic humic water, and lake waters were investigated in the dark and in a growth chamber outfitted with fluorescent lamps simulating the UV output of sunlight at 25 degrees C. No significant hydrolytic degradation/isomerization was observed for 30 days in all aqueous solutions. However, fluvoxamine was moderately isomerized to its (Z)-isomer by simulated sunlight. The photo-isomerization occurred in two stages. The photo-isomerization occurred rapidly within the first 7 days and slowly thereafter with a rate constant of 0.12-0.19 day(-1) for the first stage and 0.04-0.05 day(-1) for the second stage. Photosensitized rate constants in synthetic humic water and in lake waters were approximately 6-7 times faster than that in pH 9 buffer with the rate constants of 1.15-1.34 day(-1) in the first stage. The (Z)-isomer of fluvoxamine was the only product detected in all aqueous solutions and was identified using LC-ESI-MS.

Degradation of citalopram by simulated sunlight.

Citalopram (CIT), 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-5-phthalancarbonitrile, a selective serotonin reuptake inhibitor, is one of the most widely used antidepressants for the treatment of anxiety, obsessional, and control disorders. The degradation of the pharmaceutical CIT hydrogen bromide in water was investigated in the dark and in a growth chamber outfitted with fluorescent lamps simulating the ultraviolet output of sunlight at 25 degrees C. No significant degradation could be detected in dark controls in any aqueous solution investigated over a period of 30 d. Citalopram degraded less than 0.5% at pH 5 and pH 7 during the 30-d exposure period under simulated sunlight. However, at pH 9, CIT moderately degraded, with a half-life of 65 d via a pseudo-first order kinetic model. Degradation was faster in synthetic humic water (half-life, 24 d) and in natural waters (half-lives, 14 and 43 d) than in pH 9 buffer, indicating photosensitization by humic acid or other materials in water. Two photoproducts were detected over the irradiation period, and their structures were identified as N-desmethylcitalopram (DCIT) produced by N-demethylation as a major product and CIT N-oxide by N-oxygenation as a minor product by liquid chromatography-electrospray ionization-mass spectrometry. The DCIT appeared to be hydrolytically and photolytically stable in aqueous environments. In conclusion, CIT and DCIT were relatively stable in various solutions including natural waters. However, they may dissipate from the aqueous phase to some extent, possibly because of adsorption in real environments where soils and sediments exist.

Hydrolysis and photolysis of paroxetine, a selective serotonin reuptake inhibitor, in aqueous solutions.

The hydrolysis and photolysis of paroxetine HCI, a selective serotonin reuptake inhibitor, in aqueous buffer solutions (pH 5, 7, and 9), in synthetic humic water, and in lake water were investigated at 25 degrees C in the dark and in a growth chamber outfitted with fluorescent lamps simulating the ultraviolet (UV) output of sunlight. Paroxetine was degraded completely within 4 d by simulated sunlight in all aqueous media. Photolysis of paroxetine HCI was accelerated by increasing pH. The t1/2 values at pH 5, 7, and 9 were 15.79, 13.11, and 11.35 h, respectively. The half-lives of paroxetine in synthetic humic water and two lake waters were slightly longer than in pH 7 buffer. Two photoproducts were detected and their structures were identified by liquid chromatography-mass spectrometry in positive mode. Photoproduct I was found to be photolytically unstable, being gradually degraded after 12 to 18 h of irradiation. However, photoproduct II was photolytically very stable throughout the experiment period, indicating that it was persistent to further photodegradation. In the dark, paroxetine in all aqueous solutions was found to be stable over a 30-d period. In conclusion, paroxetine is a relatively photolabile drug that has a possibility of photodegradation by sunlight in surface water.

Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia.

Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac; fluvoxamine, Luvox; paroxetine, Paxil; citalopram, Celexa; and sertraline, Zoloft) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment.

Hydrolysis and photolysis of flumioxazin in aqueous buffer solutions.

To determine the degradation rates and degradation products of the herbicide flumioxazin in aqueous buffer solutions (pH 5, 7 and 9), its hydrolysis and photolysis were investigated at 30 degrees C in the dark, and in a growth chamber fitted with fluorescent lamps simulating the UV output of sunlight. The rate of hydrolysis of flumioxazin was accelerated by increasing pH. The t(1/2) values at pH 5, 7 and 9 were 16.4, 9.1 and 0.25 h, respectively. Two degradation products were detected and their structural assignments were made on the basis of LC-MS data. Degradation product I was detected in all buffer solutions while degradation product II was detected in acidic buffer only. Both degradation products appeared to be stable to further hydrolysis. After correcting for the effects of hydrolysis, the photolytic degradation rate also increased as a function of pH and was approximately 10 times higher at pH 7 than that at pH 5, showing t(1/2) values of 4.9 and 41.5 h, respectively. Degradation products formed by photolysis were the same as those formed by hydrolysis. Flumioxazin was degraded more extensively at high pH and should degrade in surface water.

Fate of triclosan and triclocarban in soil columns with and without biosolids surface application.

The leaching and transformation behaviors of triclosan (TCS) and triclocarban (TCC) in soil columns (20 cm high, 4 cm in diameter) packed with an agricultural soil (Roxana very fine sandy loam) with and without biosolids surface application were investigated. The column leachates and soil samples were analyzed for TCS, TCC, and their transformation products. Significantly more TCS was transformed compared with TCC. Surface application of biosolids significantly retarded their transformation. Downward movement of TCS and TCC occurred within a 10-cm soil depth. Methyl-TCS was not detectable in the leachates but was detected in the top 5-cm soil layer, with more appearing in the biosolids-applied soil. At the end of the column study, carbanilide (CBA) was the only detectable TCC reductive dechlorination product in the soil. No TCC reductive dechlorination products were detectable in the leachates. Detection of 3,4-dichloroaniline (3,4-DCA) and 4-chloroaniline (4-CA) suggested the occurrence of TCC hydrolysis. Rapid leaching of 4-CA through the soil column was observed. The 3,4-DCA was detected throughout the entire 20-cm depth of the soil column but not in the leachates. The fact that only small percentages of the transformed TCS and TCC appeared, after a 101-d column study, in the forms of the products analyzed suggested that either the investigated transformation pathways were minor pathways or further rapid transformation of those products had occurred.

Aqueous solubility, n-octanol-water partition coefficient, and sorption of five selective serotonin reuptake inhibitors to sediments and soils.

Aqueous solubilities (S (w)) and n-octanol-water partition coefficients (K (ow)) of five selective serotonin reuptake inhibitors (SSRIs) were measured and sorption to two sediments and three soils with organic matter contents ranging from 0.16% to 1.77% and pH ranging between 5.0 and 7.8 was investigated using a batch equilibrium method. SSRIs had high S (w) (3,022-15,460 mg/l) and relatively low log K (ow) (1.12-1.39). Sorption isotherms followed the Freundlich equation. All SSRIs had sorption capacities of greater than 91% except fluvoxamine with a minimum capacity of 73%. Organic matter contents partly affected sorption, however no correlation between sorption characteristics and cation exchange capacity (CEC) or clay content was observed for any SSRI or adsorbent. Values of K (f), K (d), and log K (oc) ranged from 39 to 18,342, from 60 to 42,579, and 3.35 to 6.02 for the SSRIs. SSRIs likely exhibit mixed mechanisms of sorption such as ionic binding in addition to hydrophobic interactions.