The PD Reflects Selection of Nontarget Locations, Not Distractor Suppression.

In visual search tasks, negative features provide information about stimuli that can be excluded from search. It has been shown that these negative features help participants to locate the target, possibly by attentional suppression of stimuli sharing the negative feature. Attentional suppression is assumed to be reflected in an event-related potential, the PD component. To provide a further test of these assumptions, we presented the color of the distractor at the start of a trial and asked participants to find the other colored stimulus in the subsequent search display. Consistent with attentional suppression, we observed a PD to a lateral distractor shown with a vertical target. However, the PD occurred in this condition only when target and distractor could also be on opposite sides of fixation. The effect of trial context on the PD suggests that the PD reflects a search strategy whereby participants select stimuli opposite to the distractor when trials with opposite placements occur during the experiment. Therefore, the PD to the distractor may in fact be an N2pc to the opposite stimulus, indicating that the distractor is not suppressed, but avoided by redirecting attentional selection to the opposite side.

Hybrid Vesicles Enable Mechano-Responsive Hydrogel Degradation.

Stimuli-responsive hydrogels are intriguing biomimetic materials. Previous efforts to develop mechano-responsive hydrogels have mostly relied on chemical modifications of the hydrogel structures. Here, we present a simple, generalizable strategy that confers mechano-responsive behavior on hydrogels. Our approach involves embedding hybrid vesicles, composed of phospholipids and amphiphilic block copolymers, within the hydrogel matrix to act as signal transducers. Under mechanical stress, these vesicles undergo deformation and rupture, releasing encapsulated compounds that can control the hydrogel network. To demonstrate this concept, we embedded vesicles containing ethylene glycol tetraacetic acid (EGTA), a calcium chelator, into a calcium-crosslinked alginate hydrogel. When compressed, the released EGTA sequesters calcium ions and degrades the hydrogel. This study provides a novel method for engineering mechano-responsive hydrogels that may be useful in various biomedical applications.

Biased Competition between Targets and Distractors Reduces Attentional Suppression: Evidence from the Positivity Posterior Contralateral and Distractor Positivity.

The biased competition account claims that competition between two stimuli increases when they are close together compared with when they are far apart. The reason is that nearby stimuli are more likely to be represented in the same receptive fields, requiring top-down or bottom-up biases to resolve the ambiguity. Consistent with biased competition, previous research showed that an index of attentional enhancement, the N2pc component, was attenuated when two targets were close together. In contrast, it is unclear whether distractor processing would also be attenuated when the distractor is close to the target. To answer this question, we used the additional singleton paradigm where a target is sometimes accompanied by a more salient, but entirely irrelevant, distractor. In the conditions of interest, the distance between the target and the distractor was systematically manipulated whereas the eccentricity to central fixation was always the same. The results showed that two indices of attentional suppression, the positivity posterior contralateral and distractor positivity components, were attenuated when the distractor was close to the target. Consistent with biased competition, attentional suppression of distractors was inhibited when the distance between target and distractor was short. The reduced attentional suppression of distractors with nearby targets may contribute to the increased behavioral interference with close distractors.

Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome.

Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment. Through a combination of autozygosity mapping and whole-exome sequencing, we identified WDR73 as a gene in which mutations cause Galloway-Mowat syndrome in two unrelated families. WDR73 encodes a WD40-repeat-containing protein of unknown function. Here, we show that WDR73 was present in the brain and kidney and was located diffusely in the cytoplasm during interphase but relocalized to spindle poles and astral microtubules during mitosis. Fibroblasts from one affected child and WDR73-depleted podocytes displayed abnormal nuclear morphology, low cell viability, and alterations of the microtubule network. These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features. WDR73 is another example of a gene involved in a disease affecting both the kidney glomerulus and the CNS.

'Herbal' but potentially hazardous: an analysis of the constituents and smoke emissions of tobacco-free waterpipe products and the air quality in the cafés where they are served.

BACKGROUND: There are limited data on the composition and smoke emissions of 'herbal' shisha products and the air quality of establishments where they are smoked. METHODS: Three studies of 'herbal' shisha were conducted: (1) samples of 'herbal' shisha products were chemically analysed; (2) 'herbal' and tobacco shisha were burned in a waterpipe smoking machine and main and sidestream smoke analysed by standard methods and (3) the air quality of six waterpipe cafés was assessed by measurement of CO, particulate and nicotine vapour content. RESULTS: We found considerable variation in heavy metal content between the three products sampled, one being particularly high in lead, chromium, nickel and arsenic. A similar pattern emerged for polycyclic aromatic hydrocarbons. Smoke emission analyses indicated that toxic byproducts produced by the combustion of 'herbal' shisha were equivalent or greater than those produced by tobacco shisha. The results of our air quality assessment demonstrated that mean PM2.5 levels and CO content were significantly higher in waterpipe establishments compared to a casino where cigarette smoking was permitted. Nicotine vapour was detected in one of the waterpipe cafés. CONCLUSIONS: 'Herbal' shisha products tested contained toxic trace metals and PAHs levels equivalent to, or in excess of, that found in cigarettes. Their mainstream and sidestream smoke emissions contained carcinogens equivalent to, or in excess of, those of tobacco products. The content of the air in the waterpipe cafés tested was potentially hazardous. These data, in aggregate, suggest that smoking 'herbal' shisha may well be dangerous to health.

A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS.

Several genes, mainly involved in podocyte cytoskeleton regulation, have been implicated in familial forms of primary FSGS. We identified a homozygous missense mutation (p.P209L) in the TTC21B gene in seven families with FSGS. Mutations in this ciliary gene were previously reported to cause nephronophthisis, a chronic tubulointerstitial nephropathy. Notably, tubular basement membrane thickening reminiscent of that observed in nephronophthisis was present in patients with FSGS and the p.P209L mutation. We demonstrated that the TTC21B gene product IFT139, an intraflagellar transport-A component, mainly localizes at the base of the primary cilium in developing podocytes from human fetal tissue and in undifferentiated cultured podocytes. In contrast, in nonciliated adult podocytes and differentiated cultured cells, IFT139 relocalized along the extended microtubule network. We further showed that knockdown of IFT139 in podocytes leads to primary cilia defects, abnormal cell migration, and cytoskeleton alterations, which can be partially rescued by p.P209L overexpression, indicating its hypomorphic effect. Our results demonstrate the involvement of a ciliary gene in a glomerular disorder and point to a critical function of IFT139 in podocytes. Altogether, these data suggest that this homozygous TTC21B p.P209L mutation leads to a novel hereditary kidney disorder with both glomerular and tubulointerstitial damages.

Arylnaphthalene and aryltetralin-type lignans in hairy root cultures of Linum perenne, and the stereochemistry of 6-methoxypodophyllotoxin and one diastereoisomer by HPLC-MS and NMR spectroscopy.

INTRODUCTION: Hairy root cultures of Linum sp. are an alternative for the high production of lignans. Linum perenne is known to produce arylnaphthalene-type lignans such as justicidin B, isojusticidin and diphyllin. OBJECTIVE: To elucidate the presence of aryltetralin-type lignan diastereoisomers, besides the known arylnaphthalene-type lignans, in hairy roots of Linum perenne, and to determine the configurations of one diastereoisomer of 6-methoxypodophyllotoxin (6-MPTOX). METHODS: Lignans from hairy root cultures of Linum perenne were extracted and separated by HPLC. Arylnaphthalene-type lignans were identified by LC-MS, according to the literature. Two diastereoisomers of aryltetralin-type lignans were analysed by mass spectrometry and NMR spectroscopy. RESULTS: Numerous arylnaphthalene-type lignans (diphyllin-2-hexose-pentose, diphyllin-3-pentose and diphyllin-hexose) were identified in hairy root cultures. Methoxypodophyllotoxin, an aryltetralin-type lignan, was also identified, as well as one diastereoisomer. This aryltetralin-type lignan could be derived via 7-hydroxymatairesinol as a hypothetical biosynthetic pathway. The stereochemical configurations of aryltetralin isomers were determined. CONCLUSION: Arylnaphthalene and two diastereoisomers of aryltetralin-type lignans are produced in Linum perenne hairy root cultures. Matairesinol, the precursor of justicidin B, also seems to be converted into 6-MPTOX via 7-hydroxymatairesinol. This is the first report of the stereochemical configurations of an aryltetralin-type lignan other than podophyllotoxin (PTOX).

NPHS2 mutations in steroid-resistant nephrotic syndrome: a mutation update and the associated phenotypic spectrum.

Mutations in the NPHS2 gene encoding podocin are implicated in an autosomal-recessive form of nonsyndromic steroid-resistant nephrotic syndrome in both pediatric and adult patients. Patients with homozygous or compound heterozygous mutations commonly present with steroid-resistant nephrotic syndrome before the age of 6 years and rapidly progress to end-stage kidney disease with a very low prevalence of recurrence after renal transplantation. Here, we reviewed all the NPHS2 mutations published between October 1999 and September 2013, and also all novel mutations identified in our personal cohort and in international genetic laboratories. We identified 25 novel pathogenic mutations in addition to the 101 already described. The mutations are distributed along the entire coding region and lead to all kinds of alterations including 53 missense, 17 nonsense, 11 small insertions, 26 small deletions, 16 splicing, two indel mutations, and one mutation in the stop codon. In addition, 43 variants were classified as variants of unknown significance, as these missense changes were exclusively described in the heterozygous state and/or considered benign by prediction software. Genotype-phenotype analyses established correlations between specific variants and age at onset, ethnicity, or clinical evolution. We created a Web database using the Leiden Open Variation Database (www.lovd.nl/NPHS2) software that will allow the inclusion of future reports.

INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.

BACKGROUND: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. METHODS: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. RESULTS: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. CONCLUSIONS: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).

Workers exposed to wood dust have an increased micronucleus frequency in nasal and buccal cells: results from a pilot study.

Wood dust is recognised as a human carcinogen, based on the strong association of wood dust exposure and the elevated risk of malignant tumours of the nasal cavity and paranasal sinuses [sino-nasal cancer (SNC)]. The study aimed to assess genetic damage in workers exposed to wood dust using biomarkers in both buccal and nasal cells that reflect genome instability events, cellular proliferation and cell death frequencies. Nasal and buccal epithelial cells were collected from 31 parquet layers, installers, carpenters and furniture workers (exposed group) and 19 non-exposed workers located in Switzerland. Micronucleus (MN) frequencies were scored in nasal and buccal cells collected among woodworkers. Other nuclear anomalies in buccal cells were measured through the use of the buccal micronucleus cytome assay. MN frequencies in nasal and buccal cells were significantly higher in the exposed group compared to the non-exposed group; odds ratio for nasal cells 3.1 [95% confidence interval (CI) 1.8-5.1] and buccal cells 1.8 (95% CI 1.3-2.4). The exposed group had higher frequencies of cells with nuclear buds, karyorrhectic, pyknotic, karyolytic cells and a decrease in the frequency of basal, binucleated and condensed cells compared to the non-exposed group. Our study confirms that woodworkers have an elevated risk for chromosomal instability in cells of the aerodigestive tract. The MN assay in nasal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk. Future studies should seek to standardise the protocol for MN frequency in nasal cells similar to that for MN in buccal cells.

Impact of a smoking ban in hospitality venues on second hand smoke exposure: a comparison of exposure assessment methods.

BACKGROUND: In May 2010, Switzerland introduced a heterogeneous smoking ban in the hospitality sector. While the law leaves room for exceptions in some cantons, it is comprehensive in others. This longitudinal study uses different measurement methods to examine airborne nicotine levels in hospitality venues and the level of personal exposure of non-smoking hospitality workers before and after implementation of the law. METHODS: Personal exposure to second hand smoke (SHS) was measured by three different methods. We compared a passive sampler called MoNIC (Monitor of NICotine) badge, to salivary cotinine and nicotine concentration as well as questionnaire data. Badges allowed the number of passively smoked cigarettes to be estimated. They were placed at the venues as well as distributed to the participants for personal measurements. To assess personal exposure at work, a time-weighted average of the workplace badge measurements was calculated. RESULTS: Prior to the ban, smoke-exposed hospitality venues yielded a mean badge value of 4.48 (95%-CI: 3.7 to 5.25; n = 214) cigarette equivalents/day. At follow-up, measurements in venues that had implemented a smoking ban significantly declined to an average of 0.31 (0.17 to 0.45; n = 37) (p = 0.001). Personal badge measurements also significantly decreased from an average of 2.18 (1.31-3.05 n = 53) to 0.25 (0.13-0.36; n = 41) (p = 0.001). Spearman rank correlations between badge exposure measures and salivary measures were small to moderate (0.3 at maximum). CONCLUSIONS: Nicotine levels significantly decreased in all types of hospitality venues after implementation of the smoking ban. In-depth analyses demonstrated that a time-weighted average of the workplace badge measurements represented typical personal SHS exposure at work more reliably than personal exposure measures such as salivary cotinine and nicotine.

Lasibidoupins A and B, two new compounds from the stems of Lasianthus bidoupensis V.S. Dang & Naiki.

From the Lasianthus bidoupensis stems, two new compounds, including one new 9,10-anthraquinone, lasibidoupin A (1), and one new 6,7-benzocoumarin, lasibidoupin B (2), together with one known compound, 11-O-methyldamnacanthol (3) were isolated using chromatographic method. Their structures were determined by extensive HRMS, and NMR assignments. Compound 3 was reported for the first time from this species. New compounds (1 & 2) were tested for the cytotoxicity against three human cancer cell lines (MCF-7, HeLa, and NCI-H460) by SRB assay. As results, 1 & 2 exhibited significant cytotoxic activity against all cancer cell lines (IC50 ranged from 0.058 ± 0.003 to 0.177 ± 0.014 µM).

Exposure to tobacco smoke before and after a partial smoking ban in prison: indoor air quality measures.

UNLABELLED: Although exposure to secondhand smoke (SHS) is reportedly high in prison, few studies have measured this in the prison environment, and none have done so in Europe. We measured two indicators of SHS exposure (particulate matter PM10 and nicotine) in fixed locations before (2009) and after (2010) introduction of a partial smoking ban in a Swiss prison. Access to smoking cessation support was available to detainees throughout the study. OBJECTIVES: To measure SHS before and after the introduction of a partial smoking ban. METHODS: Assessment of particulate matter PM10 (suspended microparticles of 10 µm) and nicotine in ambient air, collected by real-time aerosol monitor and nicotine monitoring devices. RESULTS: The authors observed a significant improvement of nicotine concentrations in the air after the introduction of the smoking ban (before: 7.0 µg/m(3), after: 2.1 µg/m(3), difference 4.9 µg/m(3), 95% CI for difference: 0.52 to 9.8, p=0.03) but not in particulate matter PM10 (before: 0.11 mg/m(3), after: 0.06 mg/m(3), difference 0.06 mg/m(3), 95% CI for difference of means: -0.07 to 0.19, p=0.30). CONCLUSIONS: The partial smoking ban was followed by a decrease in nicotine concentrations in ambient air. These improvements can be attributed to the introduction of the smoking ban since no other policy change occurred during this period. Although this shows that concentrations of SHS decreased significantly, protection was still incomplete and further action is necessary to improve indoor air quality.

A simple gas chromatography method for the analysis of monoethanolamine in air.

A simple method determining airborne monoethanolamine has been developed. Monoethanolamine determination has traditionally been difficult due to analytical separation problems. Even in recent sophisticated methods, this difficulty remains as the major issue often resulting in time-consuming sample preparations. Impregnated glass fiber filters were used for sampling. Desorption of monoethanolamine was followed by capillary GC analysis and nitrogen phosphorous selective detection. Separation was achieved using a specific column for monoethanolamines (35% diphenyl and 65% dimethyl polysiloxane). The internal standard was quinoline. Derivatization steps were not needed. The calibration range was 0.5-80 µg/mL with a good correlation (R(2) = 0.996). Averaged overall precisions and accuracies were 4.8% and -7.8% for intraday (n = 30), and 10.5% and -5.9% for interday (n = 72). Mean recovery from spiked filters was 92.8% for the intraday variation, and 94.1% for the interday variation. Monoethanolamine on stored spiked filters was stable for at least 4 weeks at 5°C. This newly developed method was used among professional cleaners and air concentrations (n = 4) were 0.42 and 0.17 mg/m(3) for personal and 0.23 and 0.43 mg/m(3) for stationary measurements. The monoethanolamine air concentration method described here was simple, sensitive, and convenient both in terms of sampling and analytical analysis.

The allocation of working memory resources determines the efficiency of attentional templates in single- and dual-target search.

Attentional templates are representations of target features in working memory (WM). Although two attentional templates can guide visual search in dual-target search, search efficiency is reduced compared with one attentional template in single-target search. Here, we investigated whether the allocation of WM resources contributes to these differences. Participants always memorized two colors, but the use of the corresponding WM representations varied. In the blocked conditions, the two colors were either maintained as attentional templates for dual-target search or as simple WM representations for recall only. In the mixed condition, one color was maintained as an attentional template for single-target search and the other as a simple WM representation for recall only. Reaction times (RTs) were delayed and recall precision reduced with two attentional templates in the blocked condition compared with one attentional template in the mixed condition, indicating that search efficiency and WM resources decreased in dual- compared with single-target search. Moreover, the attentional template was always recalled more precisely than the simple WM representation in the mixed condition, despite lowered visual search frequency (Experiment 2) and retro-cueing (Experiment 3). Consistent with the existence of an "active" WM state, resources were strongly biased toward the attentional template in single-target search. In dual-target search, however, resources were balanced between two attentional templates and flexibly adjusted with retro-cues, as with two simple WM representations. Therefore, the allocation of WM resources goes beyond the traditional dichotomy between "active" and "accessory" WM states and explains how attentional templates guide visual search with variable efficiency. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Guidance of visual search by negative attentional templates depends on task demands.

Visual search for a target is faster when its features are known before the search display appears, but there is an ongoing discussion about whether knowledge of nontarget features has a similar effect. Stored target or nontarget features used to guide visual search are referred to as positive or negative attentional templates, respectively. We suggest that the inconsistent findings concerning negative attentional templates may arise from 2 methodological choices in past research. The activation of negative attentional templates was never directly assessed and the use of negative attentional templates by the participant was optional. We addressed these issues in the contingent capture paradigm, which provides a marker for the activation of attentional templates in conditions where attentional templates are optional or mandatory. If an attentional template for a color is activated, cuing effects are larger for spatial cues in a matching color than for spatial cues in a nonmatching color. The question is whether the activation of negative attentional templates results in a similar difference between matching and nonmatching colors. We found that negative attentional templates were not activated when the target could be located based on its saliency (singleton search) and the use of the negative attentional template was optional. In contrast, when the negative attentional template was necessary to locate the target (feature search), we found the expected difference between matching and nonmatching spatial cues. Thus, the activation of negative attentional templates depends on task demands. In contrast, positive attentional templates were activated irrespective of task demands. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Search mode, not the attentional window, determines the magnitude of attentional capture.

A salient color distractor is known to capture attention during search for a less salient shape target, but the mechanisms underlying attentional capture are debated. Theeuwes (2004, Psychonomic Bulletin & Review, 11(1), 65-70) argued that attentional capture depends on the size of the attentional window. If the attentional window is large, search is efficient and attentional capture should be stronger because the distractor is more likely to be inside the window. Consistently, we found higher search efficiency and more attentional capture in singleton than in feature search. However, differences in attentional capture only occurred when singleton and feature search were performed by different groups of participants, but not when singleton and feature search occurred unpredictably in the same group of participants. This result contradicts the attentional window account because search efficiency was always higher in singleton than in feature search. Rather, the results support search mode theory, which claims that participants looked for the most salient stimulus in singleton search ("singleton detection mode"), which resulted in more capture by the salient color distractor. When search types varied unpredictably, it was impossible to apply a consistent search strategy, which eliminated the differences between singleton and feature search. Further, we manipulated search efficiency by target-nontarget similarity. With dissimilar nontargets, the target was salient and search efficiency was high. Therefore, the attentional window account predicts more capture. However, we found the opposite result in singleton search and no difference in feature search. Taken together, these observations are inconsistent with the attentional window account but support search mode theory.

4D biofabrication via instantly generated graded hydrogel scaffolds.

Formation of graded biomaterials to render shape-morphing scaffolds for 4D biofabrication holds great promise in fabrication of complex structures and the recapitulation of critical dynamics for tissue/organ regeneration. Here we describe a facile generation of an adjustable and robust gradient using a single- or multi-material one-step fabrication strategy for 4D biofabrication. By simply photocrosslinking a mixed solution of a photocrosslinkable polymer macromer, photoinitiator (PI), UV absorber and live cells, a cell-laden gradient hydrogel with pre-programmable deformation can be generated. Gradient formation was demonstrated in various polymers including poly(ethylene glycol) (PEG), alginate, and gelatin derivatives using various UV absorbers that present overlap in UV spectrum with that of the PI UV absorbance spectrum. Moreover, this simple and effective method was used as a universal platform to integrate with other hydrogel-engineering techniques such as photomask-aided microfabrication, photo-patterning, ion-transfer printing, and 3D bioprinting to fabricate more advanced cell-laden scaffold structures. Lastly, proof-of-concept 4D tissue engineering was demonstrated in a study of 4D bone-like tissue formation. The strategy's simplicity along with its versatility paves a new way in solving the hurdle of achieving temporal shape changes in cell-laden single-component hydrogel scaffolds and may expedite the development of 4D biofabricated constructs for biological applications.

Statistical learning in visual search reflects distractor rarity, not only attentional suppression.

In visual search tasks, salient distractors may capture attention involuntarily, but interference can be reduced when the salient distractor appears more frequently on one out of several possible positions. The reduction was attributed to attentional suppression of the high-probability position. However, all previous studies on this topic compared performance on the high-probability position to the remaining positions, which had a low probability of containing the distractor. Therefore, it is not clear whether the difference resulted from reduced interference on the high-probability position or from increased interference on the low-probability positions. To decide between these alternatives, we compared high-probability and low-probability with equal-probability positions. Consistent with attentional suppression, interference was reduced on the high-probability position compared with equal-probability positions. However, there was also an increase in interference on low-probability positions compared with equal-probability positions. The increase is in line with previous reports of boosted interference when distractors are rare. Our results show that the experimental design used in previous research is insufficient to separate effects of attentional suppression and those of distractor rarity.

Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 µg/L and 1 to 50 µg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 µg/L in urine and 1.47 µg/L in plasma for THPI and 1.14 and 2.17 µg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine.