Plastics are now omnipresent in our daily lives. The existence of microplastics (1 µm to 5 mm in length) and possibly even nanoplastics (<1 μm) has recently raised health concerns. In particular, ...nanoplastics are believed to be more toxic since their smaller size renders them much more amenable, compared to microplastics, to enter the human body. However, detecting nanoplastics imposes tremendous analytical challenges on both the nano-level sensitivity and the plastic-identifying specificity, leading to a knowledge gap in this mysterious nanoworld surrounding us. To address these challenges, we developed a hyperspectral stimulated Raman scattering (SRS) imaging platform with an automated plastic identification algorithm that allows micro-nano plastic analysis at the single-particle level with high chemical specificity and throughput. We first validated the sensitivity enhancement of the narrow band of SRS to enable high-speed single nanoplastic detection below 100 nm. We then devised a data-driven spectral matching algorithm to address spectral identification challenges imposed by sensitive narrow-band hyperspectral imaging and achieve robust determination of common plastic polymers. With the established technique, we studied the micro-nano plastics from bottled water as a model system. We successfully detected and identified nanoplastics from major plastic types. Micro-nano plastics concentrations were estimated to be about 2.4 ± 1.3 × 10
particles per liter of bottled water, about 90% of which are nanoplastics. This is orders of magnitude more than the microplastic abundance reported previously in bottled water. High-throughput single-particle counting revealed extraordinary particle heterogeneity and nonorthogonality between plastic composition and morphologies; the resulting multidimensional profiling sheds light on the science of nanoplastics.
The majority of exposures to engineered nanomaterials (ENM) are unintentional through occupational or domestic use; however ENM biomedical platforms are being developed for use in individualized ...and/or tissue‐targeted treatments. The placenta has been described as a barrier organ, yet maternal treatments are limited during pregnancy to diminish untoward fetal effects and direct fetal therapies are rare. While negative maternal and fetal effects have been described after ENM exposure during gestation, it is unclear if these are due to direct ENM transfer into the fetal compartment or if the placental barrier protects the fetus from direct particle exposure. Therefore, the purpose of this study was to identify ENM translocation after maternal pulmonary exposure to the fetal compartment.
Sprague‐Dawley rats were exposed to 2974 μg (2.4 × 1013 particles; calculated deposition of 952 ug/dose) of Rhodamine‐labeled 20nm polystyrene (NANOCS) in 300μL or saline control via intratracheal instillation every other day from GD 5 to GD 19. An acute group was also included, with a single ENM exposure on GD19. Animals were exposed to many optical imaging techniques (CT, FX‐Pro optical imaging, and ultrasound), in either the whole animal or dissected tissues on GD 20. Litter health was affected as evidenced by significantly higher rates of reabsorption sites in the exposed dams (18‐fold, chronic; 7‐fold, acute) compared to control. Overall, we were able to identify significantly higher optical intensity measurements in many secondary organs of the exposed animals, indicative of particle translocation from the lung. These included significantly increased optical imaging intensities in the chronic group vs the controls in the placenta (142% ± 78), whole fetal pup (144% ± 17), and in situ fetal liver (146% ± 13). Interestingly even those acutely exposed (24h prior) were also significantly different than control. These were identified as the mother's heart (156% ± 8), spleen (158% ± 6), placenta (142% ± 78), fetal heart (177% ± 37), fetal liver (both excised (190% ± 14) and within body (164% ± 10)), and whole pup (157% ± 13). Using novel placental perfusion methodology, where a placental unit is isolated, dissected, cannulated and perfused (80 mmHg maternal artery and 50 mmHg fetal umbilical artery), ENM introduced in the maternal artery can be quantified within 102 ± 13 minutes from the fetal umbilical vein effluent.
Using molecular imaging techniques, we were able to conclusively identify ENM translocation from the maternal lungs to the fetal compartment. These findings may be both beneficial and toxicological depending on the purpose of the ENM exposure. ENM transfer to the fetal compartment may allow for direct fetal treatment with the use of ENM‐based biomedical devices; in contrast the placenta may not be considered a barrier to ENM, with direct fetal contact also occurring after unintentional maternal ENM exposures.
Support or Funding Information
NIH‐R00‐ES024783 (PAS); P30‐ES005022
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Discharge summaries are important medical documents that summarise a patient’s hospital admission. The Royal College of Physicians provides standardised guidance on the content of discharge ...summaries, given their important role as a handover document to general practitioners (GPs). Our project started in June 2020 on an acute medical ward, where significant variation had been noted in the quality and content of discharge summaries. A multidisciplinary team (MDT) was formed including doctors, nurses and hospital/community pharmacists, as well as a patient representative, to ensure active patient co-design. The problem was scoped by asking GPs to provide feedback via surveys and process mapping. Our aim was to increase the compliance of discharge summaries with 10 core criteria from a baseline of 55% to 95% by June 2021. Change ideas were developed by the MDT and were tested using plan–do–study–act (PDSA) cycles that included additional pharmacy support, a discharge summary template and individualised feedback. The project reached its goal of 95% compliance in January 2021, 5 months ahead of the target date, and this improvement has been sustained since. The project expanded to a second acute medical unit ward in May 2021. The expanded project reached its goal of 90% compliance within 6 weeks and maintained sustained improvement with further PDSA cycles. A standard operating procedure has been created to help embed the changes on these wards. Our future aims are to redesign and improve the current electronic system and to help spread positive changes throughout the Trust.
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New biomedical applications involving engineered nanomaterials, along with increasing use in consumer products, makes the evaluation of the toxicological properties of these materials ...very important. This study identified how gestational exposure to nano‐TiO
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can have an impact on cardiac function to growing progeny. Maternal exposure with nano‐TiO
2
was conducted in Sprague Dawley rats which were exposed to aerosols (~10 mg/m
3
, 130 – 150 nm count median aerodynamic diameter) beginning at gestational day 5–6 for 7–8 nonconsecutive days. Three time points were used in the study, fetal (gestational day 20), neonatal (4–10 days), and young adult (6–12 weeks), to evaluate physiological, metabolic, and molecular consequences of nano‐TiO
2
gestational exposure. Techniques were employed to assess Cardiac function (echocardiography, speckle‐tracking based strain, and cardiomyocyte contractility), cardiomyocyte metabolism (Seahorse bioanalysis and electron transport chain expression and activity), and molecular changes involved in fatty acid oxidation and cellular stress (Western blotting and quantitative PCR) evaluated functional differences in gestational exposed progeny. The results of the study showed a decrease in the cardiac function of the experimental group: decreased E and A wave velocities with a 15% higher E/A ratio and a ~30% decrease in total contractility, departure velocity, and area of contraction in cardiomyocytes. Metabolically, a significant increase in proton leak, accompanied by decreases in basal respiration, maximal respiration, and spare capacity and negatively impacted electron transport chain complex I and IV activities showed altered metabolic profiles in the gestational exposed progeny. Molecular data also suggested that an increase in fatty acid metabolism, uncoupling, and cellular stress proteins may be associated with functional deficits of the heart. In conclusion, gestational nano‐TiO
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exposure considerably impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction. Histone modifications through epigenetic regulation also show changes in progeny molecular expression after maternal exposure to nano‐TiO
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, providing direction for future studies.
Support or Funding Information
This work was supported by a National Science Foundation IGERT: Research and Education in Nanotoxicology at West Virginia University Fellowship 1144676 awarded to QAH. This work was supported by the National Institutes of Health from the National Heart, Lung and Blood Institute R56 HL128485 awarded to JMH. This work was supported by the National Institutes of Health from the National Institute of Environmental Safety and Health R01 ES015022 awarded to TRN. This work was supported by an American Heart Association Predoctoral Fellowship (AHA 13PRE16850066) awarded to CEN. This work was supported by the National Institutes of Health from the National Institute of Environmental Safety and Health K99 ES024783 awarded to PAS. Small animal imaging and image analysis were performed in the West Virginia University Animal Models & Imaging Facility (AMIF), which has been supported by the WVU Cancer Institute and NIH grants P20 RR016440, P30 GM103488 and S10 R026378. Seahorse data acquisition was supported by the West Virginia Stroke CoBRE P20 GM109098.
Cardiovascular disease has a number of risk factors and confounding variables associated with the development and progression of the condition. Hypercholesterolemia is one of the few independent risk ...factors of peripheral vascular disease (PVD) and coronary artery disease (CAD) with causes stemming from a genetic predisposition and lifestyle management. The primary symptom of these diseases can be described as an endothelial cell dysfunction, which hypercholesterolemia can exacerbate, leading to a pro-inflammatory state of elevated oxidant stress and significant reduction in nitric oxide (NO) bioavailability, a key mediator of endothelium-dependent dilation. This environment can culminate into an impairment of the vascular reactivity due to mechanical and metabolic alterations. The mechanical microvascular remodeling is evident within dyslipidemia producing a decrease in vascular perfusion; however there are significant differences between the remodeling within the condition of hypercholesterolemia leading to an early evolution of MCP-1 and increased wall stiffness and thickness and later progression of hyperlipidemia leading to an increase in TNF-α and microvascular rarefaction. While the reduction in NO bioavailability, due to a reduced production or oxidative scavenge, leads to a maintained yet altered mechanism of peripheral skeletal muscle arteriolar endothelium dependent dilation with a shift to the reliance on increased production of metabolites of arachidonic acid metabolism, via the cyclooxygenase and lipoxygenase enzymatic pathways. These metabolites include 12- and 15-lipoxygenase and prostacyclin, with strong dilator effects, in addition to, thromboxane A2 a profound vasoconstrictor. The culmination of these products leads to a net reduced dilator effect evident in animals with genetic hypercholesterolemia. Current interventions include a number of cholesterol lowering prescriptions and the inclusion of a regular exercise program, which have been shown to reduce cholesterol and improve the cardiovascular symptoms. Considerable attention has been given to the molecular mechanisms leading to the improvement of microvascular endothelial dysfunction and subsequent vascular reactivity; however the mechanistic consequences of these treatments are not well understood within the realms of inflammation, oxidative stress, and vascular reactivity. In both the hypercholesterolemic and normocholesterolemic groups the greatest benefit, with respect to inflammation and oxidant stress, was seen in the exercise only groups. Unexpectedly, the hypercholesterolemic groups saw no improvement in vascular reactivity to any of the interventions; while the normocholesterolemic group presented detrimental results to the vascular reactivity of the pharmaceutically treated animals. Therefore, the mechanistic and mechanical outcomes associated with the reported pleiotropic effects of the cholesterol lowering treatments warrants further study specific to hyper- and normocholesterolemic conditions.
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