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•Wastes from leather production are upcycled as sustainable fillers for polymer composites.•Leather waste is an adjuvant and synergist to phosphorus flame retardants that decrease the ...fire load of poly(ethylene–vinyl acetate).•The main modes of action, which include enhanced residue formation and stabilization, are explored and characterized multi-methodically.•The combination of flame retardant and filler exhibit better fire performance than equal loadings of only flame retardant.•The chemical mechanisms of flame retardancy are elucidated to explain the fire phenomena.
Leather is among the most ancient, widely used materials worldwide. Industrial-scale leather production produces large quantities of organic waste attained during shaving and buffing steps during processing. In this study, leather wastes (LW) are used as fillers in flame retarded polymer composites. LW is investigated as a multifunctional bio-filler that enhances the fire performance of flame retarded poly(ethylene–vinyl acetate) (EVA) containing phosphorus flame retardants (P-FRs) ammonium polyphosphate (APP) or a melamine-encapsulated APP (eAPP). Using LW from tanneries as adjuvants to enhance P-FRs in EVA reduces industrial wastes that otherwise require costly waste management solutions. Materials are characterized multi-methodically via mechanical tests, electron microscopy, rheology, thermogravimetric analysis, evolved gas analysis, and condensed phase FTIR, also reaction-to-small-flames and cone calorimeter tests. EVA containing 10 wt-% LW and 20 wt-% P-FRs achieve 20% reductions in fire loads versus EVA, and up to 10% reduction in effective heats of combustion versus EVA with equal (30 wt-%) P-FR loadings. Enhanced char stabilization of EVA composites with LW and P-FRs lowered peaks of heat release rates up to 53% compared to EVA, and up to 40% compared to equal P-FRs loadings. Synergisms between LW and P-FRs in EVA are quantified. A chemical decomposition mechanism is proposed.
ObjectivesThe Drug-Associated Risk Tool (DART) has been developed as a self-administered questionnaire for patients with the aim of stratifying patients according to their risk of drug-related ...problems (DRPs). We aimed to validate the ability of the questionnaire to distinguish between hospitalised patients showing lower and higher numbers of DRPs.DesignCross-sectional study assessing the questionnaire’s concurrent criterion validity.SettingFive geriatric and the associated physical and neurological rehabilitation wards of a Swiss regional secondary care hospital with 617 beds.ParticipantsWe recruited 110 patients from a total of 437 admissions. Exclusion criteria were insufficient knowledge in spoken or written German, medical conditions preventing meaningful conversations and already receiving pharmacy services.InterventionsComprehensive pharmacist-led clinical medication reviews were performed, including patient interviews, to identify potential and manifest DRPs. A cluster analysis was conducted to assess the discriminatory potential of the DART to group patients according to number (low and high) of identified DRPs. A subsequent discriminatory function analysis was performed to reduce the number of items. We determined which DART items may be used to trigger what type of medication review.ResultsRecruited patients had a median age of 79 years and were prescribed a median of 11 drugs. Patients with a median DART score of 10 and a median of 3 DRPs represented one cluster, whereas patients with a median DART score of 15 and a median of 8 DRPs represented another cluster. Discriminatory function analysis reduced the questionnaire to five items with a moderate to strong correlation with the number of DRPs per patient (Spearman’s rank correlation ρ=0.44). Additional items were associated with patients benefiting from interviews.ConclusionsAs a self-administered questionnaire for patients, the DART may be used to stratify hospitalised non-acute older patients in groups of having low and high likelihood of DRPs. The analyses showed that a short form of the DART can be used instead of the full tool to identify older inpatients at risk for DRPs. Additional eight items from the DART may be used to initiate additional clinical pharmacy services. The linkage between certain DART questions and type of medication review enables pharmacist resource allocation.
The ubiquity of polymeric materials in daily life comes with an increased fire risk, and sustained research into efficient flame retardants is key to ensuring the safety of the populace and material ...goods from accidental fires. Phosphorus, a versatile and effective element for use in flame retardants, has the potential to supersede the halogenated variants that are still widely used today: current formulations employ a variety of modes of action and methods of implementation, as additives or as reactants, to solve the task of developing flame‐retarding polymeric materials. Phosphorus‐based flame retardants can act in both the gas and condensed phase during a fire. This Review investigates how current phosphorus chemistry helps in reducing the flammability of polymers, and addresses the future of sustainable, efficient, and safe phosphorus‐based flame‐retardants from renewable sources.
The burning issue: The ubiquitous use of polymeric materials in daily life comes with an increased fire risk. Continued research into efficient flame retardants is key to ensuring safety. This Review investigates how modern phosphorus chemistry helps to reduce the flammability of polymers, and addresses the future of sustainable, efficient, and safe phosphorus‐based flame retardants from renewable sources.
Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein ...drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer–protein interactions and aptamer–CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.
Nucleic acid aptamers are an emerging class of synthetic ligands and have recently attracted significant attention in numerous fields. One is in biosensor development. In principle, nucleic acid ...aptamers can be discovered to recognize any molecule of interest with high affinity and specificity. In addition, unlike most ligands evolved in nature, synthetic nucleic acid aptamers are usually tolerant of harsh chemical, physical, and biological conditions. These distinguished characteristics make aptamers attractive molecular recognition ligands for biosensing applications. This review first concisely introduces methods for aptamer discovery including upstream selection and downstream truncation, then discusses aptamer-based biosensor development from the viewpoint of signal production. graphic removed
The ability to regulate cell–material interactions is important in various applications such as regenerative medicine and cell separation. This study successfully demonstrates that the binding states ...of cells on a hydrogel surface can be programmed by using hybridized aptamers and triggering complementary sequences (CSs). In the absence of the triggering CSs, the aptamers exhibit a stable, hybridized state in the hydrogel for cell-type-specific catch. In the presence of the triggering CSs, the aptamers are transformed into a new hybridized state that leads to the rapid dissociation of the aptamers from the hydrogel. As a result, the cells are released from the hydrogel. The entire procedure of cell catch and release during the transformation of the aptamers is biocompatible and does not involve any factor destructive to either the cells or the hydrogel. Thus, the programmable hydrogel is regenerable and can be applied to a new round of cell catch and release when needed.
Abstract While the discovery of highly potent biologics has led to the development of promising therapies for various human diseases, biologics can cause severe toxicity if delivered inappropriately. ...Thus, great efforts have been made to synthesize polymeric systems for safe and efficient delivery of biologics. However, the application of polymeric delivery systems is often limited by problems such as harsh reaction conditions, low drug sequestration efficiency, and difficult drug release regulation. This study was aimed at developing a superporous material system with a hydrogel and an aptamer to overcome these challenges. The results have shown that the superporous hydrogel is capable of instantaneously and fully sequestering a large amount of growth factors, owing to the presence of superporous architectures and aptamers. Moreover, the sequestering and loading procedure does not involve any harsh conditions. The release kinetics of growth factors can be molecularly modulated by either changing the binding affinity of the aptamer or by using a triggering effector. Therefore, this study presents a promising superporous material for the delivery of highly potent biologics such as growth factors for clinical applications.
Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway ...mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy.
The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay.
Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib.
Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies.
This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.
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