IMPORTANCE: Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use ...and chronic kidney disease (CKD). OBJECTIVE: To quantify the association between PPI use and incident CKD in a population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: In total, 10 482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2 were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248 751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2 from the Geisinger Health System. EXPOSURES: Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine2 (H2) receptor antagonist use was considered a negative control and active comparator. MAIN OUTCOMES AND MEASURES: Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 in the Geisinger Health System replication cohort. RESULTS: Among 10 482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio HR, 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score–matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21). CONCLUSIONS AND RELEVANCE: Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.
Keratin is a highly multifunctional biopolymer serving various roles in nature due to its diverse material properties, wide spectrum of structural designs, and impressive performance. Keratin-based ...materials are mechanically robust, thermally insulating, lightweight, capable of undergoing reversible adhesion through van der Waals forces, and exhibit structural coloration and hydrophobic surfaces. Thus, they have become templates for bioinspired designs and have even been applied as a functional material for biomedical applications and environmentally sustainable fiber-reinforced composites. This review aims to highlight keratin's remarkable capabilities as a biological component, a source of design inspiration, and an engineering material. We conclude with future directions for the exploration of keratinous materials.
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Biomaterials; Engineering materials; Materials design
Lazarus compares and discusses comic elements used for didactic purposes in two separate literary traditions: Old Testament narrative and Aristophanic Comedies. Given that humour relies on taking ...people's ideas of what is normal and making them incongruous, this volume examines these very different texts to see how they use that comic incongruity to help define what it means to be human within the hierarchy of the universe.
Arapaima scales possess a hierarchical structure capable of absorbing a considerable amount of energy before fracture. These natural dermal armors present significant potential in the sustainable ...development of cost-effective composites. This work aimed, for the first time, to analyze the impact resistance and ballistic performance of arapaima scale-reinforced epoxy composites and their potential application in multilayered armor systems (MAS). Composite plates were prepared with 20%, 30%, and 40 vol% of arapaima scales. Composite specimens were subjected to notched Izod impact and residual velocity stand-alone tests and their MAS through backface signature (BFS) tests, with their fracture surfaces studied using SEM. The Izod tests confirmed the effect of scales' volume fraction on the energy absorbed by the composites, showing an increase with volume fraction. Residual velocity tests showed that composites with 30 vol% of scales resulted in the most significant improvement in absorbed energy. All MAS formulations presented BFS depths lower than the trauma limit specified by the NIJ standard. Fractographic analysis showed that the scales' toughening mechanisms improved the composites' energy absorption capacity. The experimental results substantiate the potential use of arapaima scales as a reinforcement agent in polymeric composites, with 30 vol% being the optimal volume fraction for energy-absorbing applications.
The horse hoof wall exhibits exceptional impact resistance and fracture control due to its unique hierarchical structure which contains tubular, lamellar, and gradient configurations. In this study, ...structural characterization of the hoof wall was performed revealing features previously unknown. Prominent among them are tubule bridges, which are imaged and quantified. The hydration-dependent viscoelasticity of the hoof wall is described by a simplified Maxwell-Weichert model with two characteristic relaxation times corresponding to nanoscale and mesoscale features. Creep and relaxation tests reveal that the specific hydration gradient in the hoof keratin likely leads to reduced internal stresses that arise from spatial stiffness variations. To better understand realistic impact modes for the hoof wall in-vivo, drop tower tests were executed on hoof wall samples. Fractography revealed that the hoof wall's reinforced tubular structure dominates at lower impact energies, while the intertubular lamellae are dominant at higher impact energies. Broken fibers were observed on the surface of the tubules after failure, suggesting that the physically intertwined nature of the tubule reinforcement and intertubular matrix improves the toughness of this natural fiber reinforced composite. The augmented understanding of the structure-mechanical property relationship in dynamic loading led to the design of additively manufactured bioinspired structures, which were evaluated in quasistatic and dynamic loadings. The inclusion of gradient structures and lamellae significantly reduced the damage sustained in drop tower tests, while tubules increased the energy absorption of samples tested in compact tension. The samples most similar to the hoof wall displayed remarkably consistent fracture control properties.
The horse hoof wall, capable of withstanding large, repeated, dynamic loads, has been touted as a candidate for impact-resistant bioinspiration. However, our understanding of this biological material and its translation into engineered designs is incomplete. In this work, new features of the horse hoof wall are quantified and the hierarchical failure mechanisms of this remarkable material under near-natural loading conditions are uncovered. A model of the hoof wall's viscoelastic response, based on studies of other keratinous materials, was developed. The role of hydration, strain rate, and impact energy on the material's response were elucidated. Finally, multi-material 3D printed designs based on the hoof's meso/microstructure were fabricated and exhibited advantageous energy absorption and fracture control relative to control samples.
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BACKGROUND:Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical ...features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes.
CASE:A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab.
CONCLUSION:Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.
The jackfruit is the largest fruit on the Earth, reaching upwards of 35 kg and falling from heights of 25 m. To survive such high energy impacts, it has evolved a unique layered configuration with a ...thorny exterior and porous tubular underlayer. During compression, these layers exhibit a progressive collapse mechanism where the tubules are first to deform, followed by the thorny exterior, and finally the mesocarp layer in between. The thorns are composed of lignified bundles which run longitudinally from the base of the thorn to the tip and are embedded in softer parenchymal cells, forming a fiber reinforced composite. The mesocarp contains more lignin than any of the other layers while the core appears to contain more pectin giving rise to variations in compressive and viscoelastic properties between the layers. The surface thorns provide a compelling impact-resistant feature for bioinspiration, with a cellular structure that can withstand large deformation without failing and wavy surface features which densify during compression without fracturing. Even the conical shape of the thorns is valuable, presenting a gradually increasing surface area during axial collapse. A simplified model of this mechanism is put forward to describe the force response of these features. The thorns also distribute damage laterally during impact and deflect cracks along their interstitial valleys. These phenomena were observed in 3D printed, jackfruit-inspired designs which performed markedly better than control prints with the same mass.
Many biological materials have evolved remarkable structures that enhance their mechanical performance and serve as sources of inspiration for engineers. Plants are often overlooked in this regard yet certain botanical components, like nuts and fruit, have shown incredible potential as blueprints for improved impact resistant designs. The jackfruit is the largest fruit on Earth and generates significant falling impact energies. Here, we explore the jackfruit's structure and its mechanical capabilities for the first time. The progressive failure imparted by its multilayered design and the unique collapse mode of the surface thorns are identified as key mechanisms for improving the fruit's impact resistance. 3D printing is used to show that these structure-property benefits can be successfully transferred to engineering materials.
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Biological systems must have the capability to withstand impacts generated during collisions due to combat and defense. Thus, evolution has created complex materials’ architectures at various length ...scales that are capable of withstanding repeated, low-to-medium-velocity impacts (up to 50 m/s). In this paper, we review impact resistant biological systems with a focus on their recurrent structural design elements, material properties, and energy absorbing mechanisms. We classify these impact resistant structures at the micro- and meso-scales into layered, gradient, tubular, sandwich, and sutured and show how they construct global hierarchical, composite, porous, and interfacial architectures. Additionally, we review how these individual structures and their design parameters can provide a tailored response. We conclude with a future outlook and discussion of their potential for impact resistant bioinspired designs.
Peroxide has been considered a chemical agent that can be used to tune the properties of polymeric materials. This research evaluated the influence of different concentrations of dialkyl peroxides on ...the mechanical, thermal, and morphological properties of linear low-density polyethylene (LLDPE) and ultra-high molecular weight polyethylene (UHMWPE). The neat polymer, as well as those with the addition of 1% and 2% by mass of dialkyl peroxides, were subjected to compression molding and immersion in water for 1 h, under controlled temperatures of 90 °C. The values of the gel content found in the samples indicated that the addition of peroxide to the LLDPE and to the UHMWPE promoted the formation of a reticulated network. The structure obtained by the crosslinking led to less reorganization of the chains during the crystallization process, resulting in the formation of imperfect crystals and, consequently, in the reduction in melting temperatures, crystallization and enthalpy. The mechanical properties were altered with the presence of the crosslinker. The polymers presented had predominant characteristics of a ductile material, with the occurrence of crazing with an increased peroxide content.
The construction industry contributes enormously to the high levels of carbon dioxide on the planet. For this reason, the sector has been investing in the development of new products that reduce the ...environmental impact. This study developed a fibrous polymeric composite using industrial residues of polyethylene terephthalate (PET) fibers for application in civil construction as a cladding element. The thermal and morphological characterization of the fiber was performed using Thermogravimetry (TG) and Scanning Electron Microscopy (SEM). Composites with 1, 3, and 5% PET fibers were obtained. Mechanical, morphological properties, chemical resistance, the effect of ultraviolet radiation and water absorption of the composites were evaluated. The results were compared to parameters established by the Brazilian standard NBR 15.575-3. Fibers had a smooth surface but with small surface defects, diameter between 20 and 30 µm and thermal stability up to 325.44 °C. The addition of 5% PET fibers resulted in an increase of more than 300% in the impact resistance of the composites, but with a reduction in the flexural strength. The mechanical and chemical resistance results met the parameters established by the standard used in the study. The degradation chamber test indicated that PET fibers suffered more from exposure to ultraviolet radiation than the polymeric matrix.
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