Search

Popularized on social media, hand-moldable plastics are formed by consumers into tools, trinkets, and dental prosthetics. Despite the anticipated dermal and oral contact, manufacturers share little information with consumers about these materials, which are typically sold as microplastic-sized resin pellets. Inherent to their function, moldable plastics pose a risk of dermal and oral exposure to unknown leachable substances. We analyzed 12 moldable plastics advertised for modeling and dental applications and determined them to be polycaprolactone (PCL) or thermoplastic polyurethane (TPU). The bioactivities of the most popular brands advertised for modeling applications of each type of polymer were evaluated using a zebrafish embryo bioassay. While water-borne exposure to the TPU pellets did not affect the targeted developmental end points at any concentration tested, the PCL pellets were acutely toxic above 1 pellet/mL. The aqueous leachates of the PCL pellets demonstrated similar toxicity. Methanolic extracts from the PCL pellets were assayed for their bioactivity using the Attagene FACTORIAL platform. Of the 69 measured end points, the extracts activated nuclear receptors and transcription factors for xenobiotic metabolism (pregnane X receptor, PXR), lipid metabolism (peroxisome proliferator-activated receptor γ, PPARγ), and oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2). By nontargeted high-resolution comprehensive two-dimensional gas chromatography (GC × GC-HRT), we tentatively identified several compounds in the methanolic extracts, including PCL oligomers, a phenolic antioxidant, and residues of suspected antihydrolysis and cross-linking additives. In a follow-up zebrafish embryo bioassay, because of its stated high purity, biomedical grade PCL was tested to mitigate any confounding effects due to chemical additives in the PCL pellets; it elicited comparable acute toxicity. From these orthogonal and complementary experiments, we suggest that the toxicity was due to oligomers and nanoplastics released from the PCL rather than chemical additives. These results challenge the perceived and assumed inertness of plastics and highlight their multiple sources of toxicity.

Objective: To study the relationship between serum creatine phosphokinase and outcomes of injury in victims with electrical burns., Material and Methods: Among 40 patients with electrical injury, 7 (18%) ones underwent upper limb amputation. There were 37 (92.5%) men and 3 (7.5%) women aged 37 (28; 47) years. We analyzed total serum creatine phosphokinase and MB fraction on the first day in patients with and without amputations., Results: Total serum creatine phosphokinase exceeded the upper reference value in 11 out of 33 patients without amputation and in all 7 patients with limb amputation ( p =0.001). Patients with limb amputation had significantly higher total serum creatine phosphokinase and MB fraction ( p <0.001 and p =0.030, respectively). Logistic regression equation showed that high total serum creatine phosphokinase significantly influenced amputation rate ( p <0.001), as evidenced by odds ratio (42.7, 95% CI 3.5-514.8). ROC analysis revealed the cut-off value of total serum creatine phosphokinase (950 IU/L). Sensitivity was 100% (63; 100), specificity - 94% (86; 94), positive predictive value - 78% (49; 78), negative predictive value - 100% (92; 100)., Conclusion: Total serum creatine phosphokinase depends only on severity of electrical and flame burns. Serum creatine phosphokinase is a predictor of upper limb amputation in patients with electrical injury. Total serum creatine phosphokinase ≥ 950 IU/L is significant for upper limb amputation (in CK-MB fraction within the reference values).

Environmental chemical (EC) exposures and our interactions with them has significantly increased in the recent decades. Toxicity associated biological characterization of these chemicals is challenging and inefficient, even with available high-throughput technologies. In this report, we describe a novel computational method for characterizing toxicity, associated biological perturbations and disease outcome, called the Chemo-Phenotypic Based Toxicity Measurement (CPTM). CPTM is used to quantify the EC "toxicity score" (Z ts ), which serves as a holistic metric of potential toxicity and disease outcome. CPTM quantitative toxicity is the measure of chemical features, biological phenotypic effects, and toxicokinetic properties of the ECs. For proof-of-concept, we subject ECs obtained from the Environmental Protection Agency's (EPA) database to the CPTM. We validated the CPTM toxicity predictions by correlating 'Z ts ' scores with known toxicity effects. We also confirmed the CPTM predictions with in-vitro, and in-vivo experiments. In in-vitro and zebrafish models, we showed that, mixtures of the motor oil and food additive 'Salpn' with endogenous nuclear receptor ligands such as Vitamin D3, dysregulated the nuclear receptors and key transcription pathways involved in Colorectal Cancer. Further, in a human patient derived cell organoid model, we found that a mixture of the widely used pesticides 'Tetramethrin' and 'Fenpropathrin' significantly impacts the population of patient derived pancreatic cancer cells and 3D organoid models to support rapid PDAC disease progression. The CPTM method is, to our knowledge, the first comprehensive toxico-physicochemical, and phenotypic bionetwork-based platform for efficient high-throughput screening of environmental chemical toxicity, mechanisms of action, and connection to disease outcomes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive reserve (CR) is the ability to preserve cognitive functions in the presence of brain pathology. In the context of Alzheimer's disease (AD), patients with higher CR show better cognitive performance relative to brain damage therefore higher CR reduces the risk of dementia. There is a strong need to develop a neurophysiological biomarker of CR given the growing interest in understanding protective brain mechanisms in AD. FMRI studies indicate that frontoparietal network plays an important role in cognitive reserve. We calculated intraregional functional connectivity of lateral prefrontal cortex (FC LPFC) using functional near infrared spectroscopy (fNIRS) in the resting state of 13 healthy individuals who were also assessed for IQ and motoric skills (the Purdue Pegboard test, PPT). FC LPFC was found to positively correlate with IQ (a proxy measure of cognitive reserve) while showing a lack of or negative correlation with the PPT scores. The results demonstrate that the cost-effective, noninvasive and widely applicable fNIRS technology can be used to evaluate cognitive reserve in individuals at risk for and patients with AD with possible numerous applications in the context of healthy aging and other age-related cognitive disorders., Competing Interests: Declaration of interest None.

An approach has been developed that allows the synthesis of submicron spherical silica particles with a controlled micro-mesoporous structure possessing a large specific surface area (up to 1300 m 2 g -1 ). Particle synthesis is carried out by the hydrolysis of a mixture of various organosilanes mostly associated either with CTAB or with each other. A change in the concentration of CTAB in the reaction mixture apparently leads to a change in the formation mechanism of nuclei for the silica particle growth, which allows for varying the diameter of the synthesized particles in the range from 40-450 nm. The effect of the composition of the silica precursor ([3-(methacryloyloxy)propyl]trimethoxysilane, (3-aminopropyl)triethoxysilane and tetraethoxysilane) on the formation process and porosity of the resulting particles is studied. It was shown that by simply varying the ratio of organosilanes in the composition of the precursor, one can control the pore diameter of the particles in a wide range from 0.6-15 nm. The large-pore (up to 15 nm) silica particles are used as a matrix for the spatial distribution of luminescent carbon dots. The incorporation of carbon dots into SiO 2 particles prevents their aggregation leading to emission quenching after drying, thus allowing us to obtain highly luminescent composite particles. LEDs based on the obtained composite material show bright visible luminescence with spectral characteristics similar to that of a commercial cold white LED., (© 2021 IOP Publishing Ltd.)

A longstanding debate has surrounded the role of the motor system in speech perception, but progress in this area has been limited by tasks that only examine isolated syllables and conflate decision-making with perception. Using an adaptive task that temporally isolates perception from decision-making, we examined an EEG signature of motor activity (sensorimotor μ/beta suppression) during the perception of auditory phonemes, auditory words, audiovisual words, and environmental sounds while holding difficulty constant at two levels (Easy/Hard). Results revealed left-lateralized sensorimotor μ/beta suppression that was related to perception of speech but not environmental sounds. Audiovisual word and phoneme stimuli showed enhanced left sensorimotor μ/beta suppression for correct relative to incorrect trials, while auditory word stimuli showed enhanced suppression for incorrect trials. Our results demonstrate that motor involvement in perception is left-lateralized, is specific to speech stimuli, and it not simply the result of domain-general processes. These results provide evidence for an interactive network for speech perception in which dorsal stream motor areas are dynamically engaged during the perception of speech depending on the characteristics of the speech signal. Crucially, this motor engagement has different effects on the perceptual outcome depending on the lexicality and modality of the speech stimulus.

Environmental pollution is a threat to humans and wildlife species. Of particular concern are endocrine disrupting chemicals (EDCs). An important target of EDCs is nuclear receptors (NRs) that control endocrine and metabolic responses through transcriptional regulation. Owing in part to structural differences of NRs, adverse effects of EDCs vary significantly among species. Here, we describe a multiplexed reporter assay (the Ecotox FACTORIAL) enabling parallel assessment of compounds' effects on estrogen, androgen, thyroid, and PPARγ receptors of representative mammals, birds, reptiles, amphibians, and fish. The Ecotox FACTORIAL is a single-well assay comprising a set of species-specific, one-hybrid GAL4-NR reporter constructs transiently transfected into test cells. To harmonize cross-species assessments, we used a combination of two approaches. First, we used the same type of test cells for all reporters; second, we implemented a parallel detection of reporter RNAs. The assay demonstrated excellent quality, reproducibility, and insignificant intra-assay variability. Importantly, the EC50 values for NR ligands were consistent with those reported for conventional assays. Using the assay allowed ranking the hazard potential of environmental pollutants (e.g., bisphenols, polycyclic aromatic hydrocarbons, and synthetic progestins) across species. Furthermore, the assay permitted detecting taxa-specific effects of surface water samples. Therefore, the Ecotox FACTORIAL enables harmonized assessment of the endocrine and metabolic disrupting activity of chemicals and surface water in humans as well as in wildlife species.

Over the last two decades, the evidence has been growing that in addition to epileptic spikes high frequency oscillations (HFOs) are important biomarkers of epileptogenic tissue. New methods of artificial intelligence such as deep learning neural networks can provide additional tools for automated analysis of EEG. Here we present a Long Short-Term Memory neural network for detection of spikes, ripples and ripples-on-spikes (RonS). We used intracranial EEG (iEEG) from two independent datasets. First dataset (7 patients) was used for network training and testing. The second dataset (5 patients) was used for cross-institutional validation. 1000 events of each class (spike, RonS, ripple and baseline) were selected from the candidates initially found using a novel threshold method. Network training was performed using random selections of 50-500 events (per class) from all patients from the 1 st dataset. This 'global' network was then tested on other events for each patient from both datasets. The network was able to detect events with a good generalisability namely, with total accuracy and specificity for each class exceeding 90% in all cases, and sensitivity less than 86% in only two cases (82.5% for spikes in one patient and 81.9% for ripples in another patient). The deep learning networks can significantly accelerate the analysis of iEEG data and increase their diagnostic value which may improve surgical outcome in patients with localization-related intractable epilepsy.

While chemical analysis of contaminant mixtures remains an essential component of environmental monitoring, bioactivity-based assessments using in vitro systems increasingly are used in the detection of biological effects. Historically, in vitro assessments focused on a few biological pathways, for example, aryl hydrocarbon receptor (AhR) or estrogen receptor (ER) activities. High-throughput screening (HTS) technologies have greatly increased the number of biological targets and processes that can be rapidly assessed. Here we screened extracts of surface waters from a nationwide survey of United States streams for bioactivities associated with 69 different end points using two multiplexed HTS assays. Bioactivity of extracts from 38 streams was evaluated and compared with concentrations of over 700 analytes to identify chemicals contributing to observed effects. Eleven primary biological end points were detected. Pregnane X receptor (PXR) and AhR-mediated activities were the most commonly detected. Measured chemicals did not completely account for AhR and PXR responses. Surface waters with AhR and PXR effects were associated with low intensity, developed land cover. Likewise, elevated bioactivities frequently associated with wastewater discharges included endocrine-related end points ER and glucocorticoid receptor. These results underscore the value of bioassay-based monitoring of environmental mixtures for detecting biological effects that could not be ascertained solely through chemical analyses.

Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging technique of growing interest as a tool for investigation of cortical activity. Due to the on-head placement of optodes, artifacts arising from head motion are relatively less severe than for functional magnetic resonance imaging (fMRI). However, it is still necessary to remove motion artifacts. We present a novel motion correction procedure based on robust regression, which effectively removes baseline shift and spike artifacts without the need for any user-supplied parameters. Our simulations show that this method yields better activation detection performance than 5 other current motion correction methods. In our empirical validation on a working memory task in a sample of children 7-15 years, our method produced stronger and more extensive activation than any of the other methods tested. The new motion correction method enhances the viability of fNIRS as a functional neuroimaging modality for use in populations not amenable to fMRI., (Copyright © 2018 Elsevier Inc. All rights reserved.)