Real-time multi-contrast magnetic particle imaging for the detection of gastrointestinal bleeding.

Gastrointestinal bleeding, as a potentially life-threatening condition, is typically diagnosed by radiation-based imaging modalities like computed tomography or more invasively catheter-based angiography. Endoscopy enables examination of the upper gastrointestinal tract and the colon but not of the entire small bowel. Magnetic Particle Imaging (MPI) enables non-invasive, volumetric imaging without ionizing radiation. The aim of this study was to evaluate the feasibility of detecting gastrointestinal bleeding by single- and multi-contrast MPI using human-sized organs. A 3D-printed small bowel phantom and porcine small bowel specimens were prepared with a defect within the bowel wall as the source of a bleeding. For multi-contrast MPI, the bowel lumen was filled with an intestinal tracer representing an orally administered tracer. MPI was performed to evaluate the fluid exchange between the vascular compartment of the bowel wall and the lumen while a blood pool tracer was applied. Leakage of the blood pool tracer was observed to the bowel lumen. Multi-contrast MPI enabled co-registration of both tracers at the same location within the bowel lumen indicating gastrointestinal bleeding. Single- and multi-contrast MPI are feasible to visualize gastrointestinal bleeding. Therefore, MPI might emerge as a useful tool for radiation-free detection of bleeding within the entire gastrointestinal tract.

Multigenerational effects of TiO2 rutile nanoparticles on earthworms.

Nanoparticles have gained considerable attention as one of the pollutants released into the environment through consumer products. This study describes the sub-chronic and generational effects of TiO2 (rutile) nanoparticles on earthworms over a 252-day duration, with exposure ranging from 0.1 to 1000 mg kg-1. Results indicate that sub-chronic exposure (28 days) of TiO2 nanoparticles did not cause notable adverse effects on the weight, reproduction, and tissue accumulation in parent earthworms. However, the F1 generation displayed remarkable growth and maturity retardation during their early developmental stages, even at lower nano-TiO2 (rutile). Significant impacts on the reproduction of the F1 generation were observed solely at the highest concentration (1000 mg kg-1), which is predicted to be below the highest exposure scenario. Moreover, long-term (252 days) exposure resulted in considerable bioaccumulation of Ti metal in the F1 generation of E. fetida. This study uncovers the negative effects of TiO2 rutile nanoparticles on earthworms across two generations, with pronounced effects on the growth, maturity, and bioaccumulation in the F1 generation compared to the parent generation. These findings suggest the potential induction of toxic effects by TiO2 rutile nanoparticles, emphasizing the sensitivity of juvenile parameters over adult parameters in toxicity assessments. Furthermore, the study highlights the urgent need for comprehensive evaluations of the longer-term toxicity of nanoparticles on terrestrial organisms. Implementing multigenerational studies will contribute significantly to a better understanding of nanoparticle ecotoxicity on environmental organisms.

Egg-yolk core-shell mesoporous silica nanoparticles for high doxorubicin loading and delivery to prostate cancer cells.

Mesoporous silica-based nanoparticles (MSNs) have gained rapid interest as a drug delivery system (DDS) and demonstrated their versatility in delivering drugs for the treatment of various cancers. However, the drug loading efficiency of MSNs is low and is usually improved by improving textural properties through complicated synthesis methods or by post synthesis modification of the surface that can result in the loss of surface area and modify its drug release properties. In this study, we report a direct single-step synthesis of MSNs with a unique egg-yolk core-shell morphology, large pore volume and a hydrophilic surface, decorated with nitrogen rich surface functionalities for increasing its drug loading capacity. This combination of excellent textural properties and surface functionalisation was achieved by a simple soft templating method using dual surfactants and the silica sources assisted by employing either triethylamine (TEA) or triethanolamine (TEO) as the hydrolysis agent. The morphology and well-ordered mesoporous structure can simply be tuned by changing the pH of the synthesis medium that affects the self-assembly mechanism of the micelles. HRTEM image of samples clearly revealed an egg-yolk core-shell morphology with a thin mesoporous silica shell. The optimised MSN samples synthesized at a pH of 11 using either TEA or TEO depicted a higher doxorubicin (Dox) loading capacity of 425 µg mg-1 and 481 µg mg-1 respectively, as compared to only 347 µg mg-1 for MSN samples due to the uniform distribution of nitrogen functionalities. The anticancer activity of Dox loaded MSNs evaluated in two different prostate cancer cell lines (PC-3 and LNCaP) showed a higher cytotoxicity of the drug loaded on optimised MSN samples as compared to pristine MSNs without affecting the cellular uptake of the particles. These results suggest that the unique single-step synthesis and functionalisation method resulted in successfully achieving higher drug loading in egg-yolk core-shell nitrogen functionalised MSNs and could be implemented as an effective carrier of chemotherapeutic drugs.

Comparative Modeling of Frequency Mixing Measurements of Magnetic Nanoparticles Using Micromagnetic Simulations and Langevin Theory.

Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.

Configurable Artificial Spin Ice with Site-Specific Local Magnetic Fields.

We demonstrate ground state tunability for a hybrid artificial spin ice composed of Fe nanomagnets which are subject to site-specific exchange-bias fields, applied in integer multiples of the lattice along one sublattice of the classic square artificial spin ice. By varying this period, three distinct magnetic textures are identified: a striped ferromagnetic phase; an antiferromagnetic phase attainable through an external field protocol alone; and an unconventional ground state with magnetically charged pairs embedded in an antiferromagnetic matrix. Monte Carlo simulations support the results of field protocols and demonstrate that the pinning tunes relaxation timescales and their critical behavior.

Silica-Based Nanoparticles as Drug Delivery Vehicles for Prostate Cancer Treatment.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers and is the fifth common cause of cancer-related mortality in men. Current methods for PCa treatment are insufficient owing to the challenges related to the non-specificity, instability and side effects caused by the drugs and therapy agents. These drawbacks can be mitigated by the design of a suitable drug delivery system that can ensure targeted delivery and minimise side effects. Silica based nanoparticles (SBNPs) have emerged as one of the most versatile materials for drug delivery due to their tunable porosities, high surface area and tremendous capacity to load various sizes and chemistry of drugs. This review gives a brief overview of the diagnosis and current treatment strategies for PCa outlining their existing challenges. It critically analyzes the design, development and application of pure, modified and hybrid SBNPs based drug delivery systems in the treatment of PCa, their advantages and limitations.

Persistence of the parabens in soil and their potential toxicity to earthworms.

Due to their antimicrobial activity, parabens are commonly used as preservatives in a variety of consumer goods including cosmetics, pharmaceuticals, and personal care products. During the production, usage and disposal of these products, parabens are released into the environment. In this study, the persistence of three widely used parabens; methyl-, propyl-, and butyl paraben in soil and their toxic effects on the soil invertebrate, Eisenia fetida was investigated. The results of this study indicate that selected parabens do not negatively affect the survival, growth, and reproduction of Eisenia fetida up to 1000 mg Kg-1 concentration. Further, these parabens (0-1000 mg Kg-1) exhibited a low persistence in soil with more than 90 % disappearing within three days. In contrast, only 16-54 % degradation of parabens occurred in frozen soil suggesting a microbial role in parabens degradation. This study demonstrates that methyl-, propyl-, and butyl parabens degrade rapidly in the terrestrial environment and therefore, are unlikely to pose a threat to species such as Eisenia fetida. To our knowledge, this is the first report on the toxicity of parabens to earthworms.

Nonequilibrium Dynamics of Magnetic Nanoparticles with Applications in Biomedicine.

Magnetic nanoparticles are currently the focus of investigation for a wide range of biomedical applications that fall into the categories of imaging, sensing, and therapeutics. A deep understanding of nanoparticle magnetization dynamics is fundamental to optimization and further development of these applications. Here, a summary of theoretical models of nanoparticle dynamics is presented, and computational nonequilibrium models are outlined, which currently represent the most sophisticated methods for modeling nanoparticle dynamics. Nanoparticle magnetization response is explored in depth; the effect of applied field amplitude, as well as nanoparticle size, on the resulting rotation mechanism and timescale is investigated. Two applications in biomedicine, magnetic particle imaging and magnetic fluid hyperthermia, are highlighted.

Purification and characterization of a novel fenamiphos hydrolysing enzyme from Microbacterium esteraromaticum MM1.

Fenamiphos is a neurotoxic organophosphorus pesticide used widely to control pests of crops. Fenamiphos and its toxic oxidation products have been detected in surface and groundwaters. A novel enzyme capable of hydrolysing P-O-C bond of fenamiphos is purified from Microbacterium esteraromaticum MM1 total cellular protein using a combination of methods. The purified fenamiphos hydrolysing enzyme (FHE) was identified as enolase (phosphopyruvate hydratase), a housekeeping enzyme with molecular mass and pI value of 45 kDa and 4.5, respectively. The optimum pH and temperature for the activity of the FHE are 7 and 25 °C, respectively. We studied the influence of metal ions and inhibitors on the enzyme activity. The enzyme was strongly activated by Mg2+ whereas Hg2+ and phenylmethyl sulfonyl fluoride (PMSF) inhibited the enzyme. The kinetic parameters, Km and Vmax for fenamiphos hydrolysis were estimated to be 584.15 ± 16.22 µM and 6.46 ± 0.13 µM min-1, respectively. The FHE was functionally active against its original substrate (2-phosphoglycerate) with Km value of 5.82 ± 1.42 µM and Vmax of 4.2 ± 0.1 µM min-1. This enzyme has great potential for its application in the detoxification of fenamiphos and its warfare homologs. To our knowledge, this is the first report on the purification of fenamiphos hydrolysing enzyme.

Data on systematic review and meta-analysis of epidemiologic evidence on the association between perineal use of talc powder and risk of ovarian cancer.

This paper describes data from a systematic review and meta-analysis [1] conducted to identify and evaluate published peer reviewed evidence on the association between perineal use of talc powder and risk of ovarian cancer. These data were collected from multiple electronic bibliographic databases, as well as from grey literature sources, without applying time, language or other filters. A meta-analysis was conducted to quantitatively assess the ovarian cancer risk in relation to talc use and other potential risk factors.

Anaerobic Microbial Degradation of Polycyclic Aromatic Hydrocarbons: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are a class of hazardous organic contaminants that are widely distributed in nature, and many of them are potentially toxic to humans and other living organisms. Biodegradation is the major route of detoxification and removal of PAHs from the environment. Aerobic biodegradation of PAHs has been the subject of extensive research; however, reports on anaerobic biodegradation of PAHs are so far limited. Microbial degradation of PAHs under anaerobic conditions is difficult because of the slow growth rate of anaerobes and low energy yield in the metabolic processes. Despite the limitations, some anaerobic bacteria degrade PAHs under nitrate-reducing, sulfate-reducing, iron-reducing, and methanogenic conditions. Anaerobic biodegradation, though relatively slow, is a significant process of natural attenuation of PAHs from the impacted anoxic environments such as sediments, subsurface soils, and aquifers. This review is intended to provide comprehensive details on microbial degradation of PAHs under various reducing conditions, to describe the degradation mechanisms, and to identify the areas that should receive due attention in further investigations.

Critical review of the association between perineal use of talc powder and risk of ovarian cancer.

Over the past four decades, there has been increasing concern that perineal use of talc powder, a commonly used personal care product, might be associated with an increased risk of ovarian cancer. OBJECTIVES: To critically review all available human epidemiological data on the relationship between perineal use of talc powder and ovarian cancer, with consideration of other relevant experimental evidence. METHODOLOGY: We identified 30 human studies for qualitative assessment of evidence, including 27 that were retained for further quantitative analysis. RESULTS: A positive association between perineal use of talc powder and ovarian cancer was found [OR: 1.28 (95% CI: 1.20-1.37)]. A significant risk was noted in Hispanics and Whites, in women applying talc to underwear, in pre-menopausal women and in post-menopausal women receiving hormonal therapy. A negative association was noted with tubal ligation. CONCLUSION: Perineal use of talc powder is a possible cause of human ovarian cancer.

Observing the colloidal stability of iron oxide nanoparticles in situ.

Colloidal processes such as nucleation, growth, ripening, and dissolution are fundamental to the synthesis and application of engineered nanoparticles, as well as numerous natural systems. In nanocolloids consisting of a dispersion of nanoparticles in solution, colloidal stability is influenced by factors including the particle surface facet and capping layer, and local temperature, chemistry, and acidity. In this paper, we investigate colloidal stability through the real-time manipulation of nanoparticles using in situ liquid cell Scanning Transmission Electron Microscopy (STEM). In a distribution of uniform iron oxide nanoparticles, we use the electron beam to precisely control the local chemistry of the solution and observe the critical role that surface chemistry plays in nanoparticle stability. By functionalizing the nanoparticle surfaces with charged amino acids and peptides, stability can be tuned to promote dissolution, growth, or agglomeration, either permanently or reversibly. STEM imaging is used to quantify kinetics of individual nanoparticles subject to local variations in chemistry. These measurements of dissolution and growth rates of iron oxide nanoparticles provide insights into nanoparticle stability relevant to synthesis and functionalization for biomedical applications.

Intracellular dynamics of superparamagnetic iron oxide nanoparticles for magnetic particle imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) are a foundational platform for a variety of biomedical applications. Of particular interest is Magnetic Particle Imaging (MPI), which is a growing area of research and development due to its advantages including high resolution and sensitivity with positive contrast. There has been significant work in the area of in vivo optimization of SPIONs for MPI as well as their biodistribution in and clearance from the body. However, little is known about the dynamics of SPIONs following cellular internalization which may limit their usefulness in a variety of potential imaging and treatment applications. This work shows a clear 20% decrease in magnetic performance of SPIONs, as observed by Magnetic Particle Spectroscopy (MPS), after internalization and systematic consideration of applicable factors that affect SPION signal generation, including microstructure, environment, and interparticle interactions. There is no observed change to SPION microstructure after internalization, and the surrounding environment plays little to no role in magnetic response for the SPIONs studied here. Interparticle interactions described by dipole-dipole coupling of SPIONs held close to one another after internalization are shown to be the dominant cause of decreased magnetic performance in cells. These conclusions were drawn from transmission electron microscopy (TEM) image analysis at relevant length scales, experimentally prepared and characterized SPIONs in varied environmental conditions, and theoretical modeling with Monte Carlo simulations.

Discriminating nanoparticle core size using multi-contrast MPI.

Magnetic particle imaging (MPI) is an imaging modality that detects the response of a distribution of magnetic nanoparticle tracers to alternating magnetic fields. There has recently been exploration into multi-contrast MPI, in which the signal from different tracer materials or environments is separately reconstructed, resulting in multi-channel images that could enable temperature or viscosity quantification. In this work, we apply a multi-contrast reconstruction technique to discriminate between nanoparticle tracers of different core sizes. Three nanoparticle types with core diameters of 21.9 nm, 25.3 nm and 27.7 nm were each imaged at 21 different locations within the scanner field of view. Multi-channel images were reconstructed for each sample and location, with each channel corresponding to one of the three core sizes. For each image, signal weight vectors were calculated, which were then used to classify each image by core size. With a block averaging length of 10 000, the median signal-to-noise ratio was 40 or higher for all three sample types, and a correct prediction rate of 96.7% was achieved, indicating that core size can effectively be predicted using signal weight vector classification with close to 100% accuracy while retaining high MPI image quality. The discrimination of the core size was reliable even when multiple samples of different core sizes were placed in the measuring field.

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals.

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61 × 10-2 and 9 × 10-4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55 × 10-1 and 8.5 × 10-3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r2 = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.

A framework for application of quantitative property-property relationships (QPPRs) in physiologically based pharmacokinetic (PBPK) models for high-throughput prediction of internal dose of inhaled organic chemicals.

New generation of toxicological tests and assessment strategies require validated toxicokinetic data or models that are lacking for most chemicals. This study aimed at developing a quantitative property-property relationship (QPPR)-based human physiologically based pharmacokinetic (PBPK) modeling framework for high-throughput predictions of inhalation toxicokinetics of organic chemicals. A PBPK model was parameterized with QPPR-derived values for hepatic clearance (CLh) and partition coefficients (P) [blood:air (Pba) and tissue:air (Pta) and tissue:blood (Ptb)]. The model was initially applied to an evaluation dataset of 40 organic chemicals in the applicability domain, and then to an expanded dataset of 249 organic chemicals from diverse chemical classes. 'Batch' analyses were performed for rapid assessments of hundreds of chemicals. The simulations of inhalation toxicokinetics following an 8-h exposure to 1 ppm of each chemical were successful. The mean ratios of their predicted-to-experimental values were within a factor of 1.36-2.36 for Ptb and 1.18 for CLh, for 80% of the chemicals in the evaluation dataset. The predicted 24-h area under the venous blood concentration-time curve (AUC24) values were within the predicted envelopes obtained while using experimental values of Pba and considering either no or maximal hepatic extraction. The reliability analysis (based on combined sensitivity and uncertainty analyses) indicated that AUC24 predictions for 55% of the expanded dataset were moderately to highly reliable, with 46% exhibiting highly reliable values. Overall, the modeling framework suggests that molecular structure and chemical properties can together be effectively used to obtain first-cut estimates of the toxicokinetics of data-poor organic chemicals for screening and prioritization purposes.

Moving table magnetic particle imaging: a stepwise approach preserving high spatio-temporal resolution.

Magnetic particle imaging (MPI) is a highly sensitive imaging method that enables the visualization of magnetic tracer materials with a temporal resolution of more than 46 volumes per second. In MPI, the size of the field of view (FoV) scales with the strengths of the applied magnetic fields. In clinical applications, those strengths are limited by peripheral nerve stimulation, specific absorption rates, and the requirement to acquire images of high spatial resolution. Therefore, the size of the FoV is usually a few cubic centimeters. To bypass this limitation, additional focus fields and/or external object movements can be applied. The latter approach is investigated. An object is moved through the scanner bore one step at a time, whereas the MPI scanner continuously acquires data from its static FoV. Using a 3-D phantom and dynamic 3-D in vivo data, it is shown that the data from such a moving table experiment can be jointly reconstructed after reordering the data with respect to the stepwise object shifts and heart beat phases.

Draft Genome Sequence of Microbacterium esteraromaticum MM1, a Bacterium That Hydrolyzes the Organophosphorus Pesticide Fenamiphos, Isolated from Golf Course Soil.

In this study, we report the first draft genome sequence of Microbacterium esteraromaticum MM1, isolated from golf course soil in South Australia. The genome possesses genes for the hydrolysis of organophosphorus (OP) pesticides and polycyclic aromatic hydrocarbon (PAH) degradation.