Recent work in science and technology studies has looked at how chemical industries manufacture doubt about the toxicity of their products and manage to establish their scientific views in the field ...of international regulations on toxic substances. Rather than examining yet another “victory” for the industry, this article analyzes the deployment of a “pro-industrial” scientific position, punctuated mainly by failure and opposition. This trajectory is tracked through the analysis of several data sets: archives, scientific documentation, and sociological interviews. The first part of the article charts the development of a biochemical concept, “peroxisome proliferation,” within an academic subfield and its subsequent appropriation by certain industrial parties who used it as a defensive weapon for their commercial interests. Through the example of the International Agency for Research on Cancer and its network of interdependent institutions, the article goes on to analyze the multiple attempts of chemical industry players to establish their interpretation of the concept within the regulatory bodies for carcinogenic substances. The study of such systems of sociological interdependence shows that a full analysis of the “doubt manufacturing” requires an examination not only of the manufacturing process but also of the reception of the ideas produced.
Material stability and dissolution in aqueous media are key issues to address in the development of a new nanomaterial intended for technological application. Dissolution phenomena affect biological ...and environmental persistence; fate, transport, and biokinetics; device and product stability; and toxicity pathways and mechanisms. This article shows that MoS2 nanosheets are thermodynamically and kinetically unstable to O2-oxidation under ambient conditions in a variety of aqueous media. The oxidation is accompanied by nanosheet degradation and release of soluble molybdenum and sulfur species, and generates protons that can colloidally destabilize the remaining sheets. The oxidation kinetics are pH-dependent, and a kinetic law is developed for use in biokinetic and environmental fate modeling. MoS2 nanosheets fabricated by chemical exfoliation with n-butyl-lithium are a mixture of 1T (primary) and 2H (secondary) phases and oxidize rapidly with a typical half-life of 1–30 days. Ultrasonically exfoliated sheets are in pure 2H phase, and oxidize much more slowly. Cytotoxicity experiments on MoS2 nanosheets and molybdate ion controls reveal the relative roles of the nanosheet and soluble fractions in the biological response. These results indicate that MoS2 nanosheets will not show long-term persistence in living systems and oxic natural waters, with important implications for biomedical applications and environmental risk.
Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and ...catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.
Multigenerational graphene oxide architectures can be programmed by specific sequences of mechanical deformations. Each new deformation results in a progressively larger set of features decorated by ...smaller preexisting patterns, indicating a structural “memory.” It is shown that these multiscale architectures are superhydrophobic and display excellent functionality as electrochemical electrodes.
Nanocomposite hydrogels that incorporate 2D carbon nanomaterials could enable augmented and responsive behaviors not observed with polymeric matrices alone. In particular, non-covalent interactions ...could facilitate enhanced mechanical performance that can be self-recovered with external stimuli. Here, we demonstrate alginate-graphene oxide (GO) hydrogels using a non-covalent, ionic crosslinking mechanism compatible with light-directed 3D printing. We show that alginate-GO hydrogels exhibit improved mechanical performance in shear, compression, and tension, including a two-fold increase in shear modulus, a three-fold decrease in inelastic deformation, and a nine-fold increase in fracture energy relative to alginate-only hydrogels. Moreover, alginate-GO hydrogels are stabilized by hydrogen bonding between nanosheets and remain intact after removal of ionic crosslinkers by chelation. As a consequence, the shear modulus of these nanocomposite hydrogels can be tuned by over 500-fold via external ion concentration. We demonstrate that alginate-GO can be stereolithographically printed into robust, freestanding and overhanging 3D structures. These designer material architectures exhibit outstanding stability and superoleophobicity in high salt solution, which can be used to repel and manipulate a variety of oils. Overall, such nanocomposite hydrogels with engineered non-covalent interactions could enable “smart” multiresponsive and multifunctional devices for aqueous and marine environments.
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Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. ...Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.
Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled‐release polymer implants ...have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery, including biocompatibility, tunable biodegradation, stabilizing effects, water‐based processing, and diverse material formats. The functional release of antibiotics spanning a range of chemical properties from different material formats of silk (films, microspheres, hydrogels, coatings) is reported. The release of penicillin and ampicillin from bulk‐loaded silk films, drug‐loaded silk microspheres suspended in silk hydrogels and bulk‐loaded silk hydrogels is investigated and the in vivo efficacy of the ampicillin‐releasing silk hydrogels is demonstrated in a murine infected‐wound model. Silk sponges with nanofilm coatings are loaded with gentamicin and cefazolin, and release is sustained for 5 and 3 days, respectively. The capability of silk antibiotic carriers to sequester, stabilize, and then release bioactive antibiotics represents a major advantage over implants and pumps based on liquid drug reservoirs, where instability at room or body temperature is limiting. The present studies demonstrate that silk biomaterials represent a novel, customizable antibiotic platform for focal delivery of antibiotics using a range of material formats (injectable to implantable).
Silk biomaterials represent a novel, customizable platform for focal antibiotic delivery with advantageous properties including biocompatibility, tunable biodegradation rate, stabilizing effects, water‐based processing, and diverse material formats. Injectable and implantable antibiotic‐releasing silk biomaterials (including hydrogels, microspheres, films, nanofilm coatings, and antibiotic‐loaded fibers) repress local bacteria growth in vitro and in vivo.
Abstract
Background
Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory ...failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far.
Methods
In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria.
Results
We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2–9.7) in the MAFP group and 17.5% (95% CI 9.6–31.4) in the group without MAFP (
p
= 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01–0.63;
p
= 0.017).
Conclusion
In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.
Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within ...three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial–mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.
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