Recent advances in in vitro models simulating the female genital tract toward more effective intravaginal therapeutic delivery.

INTRODUCTION: Intravaginal drug delivery has emerged as a promising avenue for treating a spectrum of systemic and local female genital tract (FGT) conditions, using biomaterials as carriers or scaffolds for targeted and efficient administration. Much effort has been made to understand the natural barriers of this route and improve the delivery system to achieve an efficient therapeutic response. AREAS COVERED: In this review, we conducted a comprehensive literature search using multiple databases (PubMed Scopus Web of Science Google Scholar), to discuss the potential of intravaginal therapeutic delivery, as well as the obstacles unique to this route. The in vitro cell models of the FGT and how they can be applied to probing intravaginal drug delivery are then analyzed. We further explore the limitations of the existing models and the possibilities to make them more promising for delivery studies or biomaterial validation. Complementary information is provided by in vitro acellular techniques that may shed light on mucus-drug interaction. EXPERT OPINION: Advances in 3D models and cell cultures have enhanced our understanding of the FGT, but they still fail to replicate all variables. Future research should aim to use complementary methods, ensure stability, and develop consistent protocols to improve therapy evaluation and create better predictive in vitro models for women's health.

Study of CFRP Laminate Gradually Modified throughout the Thickness Using Thin Ply under Transvers Tensile Loading.

The use of thin-ply composite materials has rapidly increased due to their tailorable mechanical properties and design flexibility. Considering an adhesively bonded composite joint, peel stress stands out as a key contributor leading to failure among other primary stress factors. Therefore, the reinforcement of carbon fiber-reinforced polymer (CFRP) laminates throughout the thickness could be considered as an approach to improve the joint strength. Using thin plies locally between the conventional CFRP layers in a laminate can enhance the strength, as the sudden change in stiffness means that the load transfer is not monotonous. Consequently, the following study examined the effect of altering thin plies gradually throughout the thickness on the behaviour of the CFRP laminates when subjected to transverse tensile loading. To achieve this goal, the CFRP laminates were gradually modified by using different commercially accessible prepreg thin plies, leading to an improved overall structural performance by reducing stress concentrations. Besides conducting an experimental study, a numerical assessment was also carried out utilizing Abaqus software with a Representative Volume Element (RVE) at the micro scale. The comparison of reference configurations, which involved various thin plies with different thicknesses and traditional CFRP laminates, with the suggested gradual configuration, demonstrated a notable enhancement in both strength and material cost. Furthermore, the proposed RVE model showed promising capability in accurately forecasting the strength of fabricated laminates.

Development of a Unified Specimen for Adhesive Characterization-Part 2: Experimental Study on the Mode I (mDCB) and II (ELS) Fracture Components.

Adhesive bonding has been increasingly employed in multiple industrial applications. This has led to a large industrial demand for faster, simpler, and cheaper characterization methods that allow engineers to predict the mechanical behavior of an adhesive with numerical models. Currently, these characterization processes feature a wide variety of distinct standards, specimen configurations, and testing procedures and require deep knowhow of complex data-reduction schemes. By suggesting the creation of a new and integrated experimental tool for adhesive characterization, it becomes possible to address this problem in a faster and unified manner. In this work, following a previous numerical study, the mode I and II components of fracture-toughness characterization were validated experimentally in two different configurations, Balanced and Unbalanced. For mode I, it was demonstrated that both configurations presented similar numerical and experimental R-curves. The relative error against standard tests was lower than ±5% for the Balanced specimen; the Unbalanced system showed higher variations, which were predicted by the numerical results. Under mode II, the Balanced specimen displayed plastic deformation due to high deflections. On the contrary, the Unbalanced specimen did not show this effect and presented a relative error of approximately ±2%. Nonetheless, it was proven that this approach to obtain such data by using a single unified specimen is still feasible but needs further development to obtain with similar precision of standard tests. In the end, a conceptual change is proposed to solve the current mode II issues.

Ternary (molybdenum disulfide/graphene)/carbon nanotube nanocomposites assembled via a facile colloidal electrostatic path as electrocatalysts for the oxygen reduction reaction: Composition and nitrogen-doping play a key role in their performance.

Nanocomposites have garnered attention for their potential as catalysts in electrochemical reactions vital for technologies like fuel cells, water splitting, and metal-air batteries. This work focuses on developing three-dimensional (3D) nanocomposites through aqueous phase exfoliation, non-covalent functionalization of building blocks with surfactants and polymers, and electrostatic interactions in solution leading to the nanocomposites assembly and organization. By combining molybdenum disulfide (MoS2) layers with graphene nanoplatelets (GnPs) to form a binary 2D composite (MoS2/GnP), and subsequently incorporating multiwalled carbon nanotubes (MWNTs) to create ternary 3D composites, we explore their potential as catalysts for the oxygen reduction reaction (ORR) critical in fuel cells. Characterization techniques such as X-ray photoelectron spectroscopy, scanning electron microscopy, and X-ray diffraction elucidate material composition and structure. Our electrochemical studies reveal insights into the kinetics of the reactions and structure-activity relationships. Both the (MoS2/GnP)-to-MWNT mass ratio and nitrogen-doping of GnPs (N-GnPs) play a key role on the electrocatalytic ORR performance. Notably, the (MoS2/N-GnP)/MWNT material, with a 3:1 mass ratio, exhibits the most effective ORR activity. All catalysts demonstrate good long-term stability and methanol crossover tolerance. This facile fabrication method and observed trends offer avenues for optimizing composite electrocatalysts further.

Assessment of environmental pollution and human health risks of mine tailings in soil: after dam failure of the Córrego do Feijão Mine (in Brumadinho, Brazil).

The dam failure of the Córrego do Feijão Mine (CFM) located in Minas Gerais State, Brazil, killed at least 278 people. In addition, large extensions of aquatic and terrestrial ecosystems were destroyed, directly compromising the environmental and socioeconomic quality of the region. This study assessed the pollution and human health risks of soils impacted by the tailing spill of the CFM dam, along a sample perimeter of approximately 200 km. Based on potential ecological risk and pollution load indices, the enrichments of Cd, As, Hg, Cu, Pb and Ni in soils indicated that the Brumadinho, Mário Campos, Betim and São Joaquim de Bicas municipalities were the most affected areas by the broken dam. Restorative and reparative actions must be urgently carried out in these areas. For all contaminated areas, the children's group indicated an exacerbated propensity to the development of carcinogenic and non-carcinogenic diseases, mainly through the ingestion pathway. Toxicological risk assessments, including acute, chronic and genotoxic effects, on people living and working in mining areas should be a priority for public management and mining companies to ensure effective environmental measures that do not harm human health and well-being over time.

Mode I Fatigue and Fracture Assessment of Polyimide-Epoxy and Silicon-Epoxy Interfaces in Chip-Package Components.

Semiconductor advancements demand greater integrated circuit density, structural miniaturization, and complex material combinations, resulting in stress concentrations from property mismatches. This study investigates the failure in two types of interfaces found in chip packages: silicon-epoxy mold compound (EMC) and polyimide-EMC. These interfaces were subjected to quasi-static and fatigue loading conditions. Employing a compliance-based beam method, the tests determined interfacial critical fracture energy values, (GIC), of 0.051 N/mm and 0.037 N/mm for the silicon-EMC and polyimide-EMC interfaces, respectively. Fatigue testing on the polyimide-epoxy interface revealed a fatigue threshold strain energy, (Gth), of 0.042 N/mm. We also observed diverse failure modes and discuss potential mechanical failures in multi-layer chip packages. The findings of this study can contribute to the prediction and mitigation of failure modes in the analyzed chip packaging. The obtained threshold energy and crack growth rate provide insights for designing safe lives for bi-material interfaces in chip packaging under cyclic loads. These insights can guide future research directions, emphasizing the improvement of material properties and exploration of the influence of manufacturing parameters on delamination in multilayer semiconductors.

Cohesive Properties of Bimaterial Interfaces in Semiconductors: Experimental Study and Numerical Simulation Using an Inverse Cohesive Contact Approach.

Examining crack propagation at the interface of bimaterial components under various conditions is essential for improving the reliability of semiconductor designs. However, the fracture behavior of bimaterial interfaces has been relatively underexplored in the literature, particularly in terms of numerical predictions. Numerical simulations offer vital insights into the evolution of interfacial damage and stress distribution in wafers, showcasing their dependence on material properties. The lack of knowledge about specific interfaces poses a significant obstacle to the development of new products and necessitates active remediation for further progress. The objective of this paper is twofold: firstly, to experimentally investigate the behavior of bimaterial interfaces commonly found in semiconductors under quasi-static loading conditions, and secondly, to determine their respective interfacial cohesive properties using an inverse cohesive zone modeling approach. For this purpose, double cantilever beam specimens were manufactured that allow Mode I static fracture analysis of the interfaces. A compliance-based method was used to obtain the crack size during the tests and the Mode I energy release rate (GIc). Experimental results were utilized to simulate the behavior of different interfaces under specific test conditions in Abaqus. The simulation aimed to extract the interfacial cohesive contact properties of the studied bimaterial interfaces. These properties enable designers to predict the strength of the interfaces, particularly under Mode I loading conditions. To this extent, the cohesive zone modeling (CZM) assisted in defining the behavior of the damage propagation through the bimaterial interfaces. As a result, for the silicon-epoxy molding compound (EMC) interface, the results for maximum strength and GIc are, respectively, 26 MPa and 0.05 N/mm. The second interface tested consisted of polyimide and silicon oxide between the silicon and EMC layers, and the results obtained are 21.5 MPa for the maximum tensile strength and 0.02 N/mm for GIc. This study's findings aid in predicting and mitigating failure modes in the studied chip packaging. The insights offer directions for future research, focusing on enhancing material properties and exploring the impact of manufacturing parameters and temperature conditions on delamination in multilayer semiconductors.

A Novel Technique for Substrate Toughening in Wood Single Lap Joints Using a Zero-Thickness Bio-Adhesive.

In contemporary engineering practices, the utilization of sustainable materials and eco-friendly techniques has gained significant importance. Wooden joints, particularly those created with polyurethan-based bio-adhesives, have garnered significant attention owing to their intrinsic environmental advantages and desirable mechanical properties. In comparison to conventional joining methods, adhesive joints offer distinct benefits such as an enhanced load distribution, reduced stress concentration, and improved aesthetic appeal. In this study, reference and toughened single-lap joint samples were investigated experimentally and numerically under quasi-static loading conditions. The proposed research methodology involves the infusion of a bio-adhesive into the wooden substrate, reinforcing the matrix of its surfaces. This innovative approach was developed to explore a synergetic effect of both wood and bio-adhesive. The experimentally validated results showcase a significant enhancement in joint strength, demonstrating an 85% increase when compared to joints with regular pine substrates. Moreover, the increased delamination thickness observed in toughened joints was found to increase the energy absorption of the joint.

Development and Study of a New Silane Based Polyurethane Hybrid Flexible Adhesive-Part 1: Mechanical Characterization.

The need for more sustainable adhesive formulations has led to the use of silane-based adhesives in different industrial sectors, such as the automotive industry. In this work, the mechanical properties of a dual cure two-component prototype adhesive which combined silylated polyurethane resin (SPUR) with standard epoxy resin was characterized under quasi-static conditions. The characterization process consisted of tensile bulk testing, to determine the Young's modulus, the tensile strength and the tensile strain to failure. The shear stiffness and shear strength were measured by performing a thick adherend shear test. The in-plane strain field was obtained using a digital image correlation method. Double-cantilever beam and mixed-mode tests were performed to assess the fracture toughness under pure modes. The prototype adhesive showed promising but lower properties compared to commercial solutions. Furthermore, the adhesive was modified via the addition of three different resin modifier additives and characterized via measuring the shear and tensile properties, but no enhancements were found. Finally, the adhesive was formulated with three different SPUR viscosities. The critical energy release rate analysis showed an optimum value for the medium viscosity SPUR adhesive.

Extended Finite Element Method (XFEM) Model for the Damage Mechanisms Present in Joints Bonded Using Adhesives Doped with Inorganic Fillers.

The use of adhesive bonding in diverse industries such as the automotive and aerospace sectors has grown considerably. In structural construction, adhesive joints provide a unique combination of low structural weight, high strength and stiffness, combined with a relatively simple and easily automated manufacturing method, characteristics that are ideal for the development of modern and highly efficient vehicles. In these applications, ensuring that the failure mode of a bonded joint is cohesive rather than adhesive is important since this failure mode is more controlled and easier to model and to predict. This work presents a numerical technique that enables the precise prediction of the bonded joint's behavior regarding not only its failure mode, but also the joint's strength, when inorganic fillers are added to the adhesive. To that end, hollow glass particles were introduced into an epoxy adhesive in different amounts, and a numerical study was carried out to simulate their influence on single lap joint specimens. The numerical results were compared against experimental ones, not only in terms of joint strength, but also their failure pattern. The neat adhesive, which showed 9% and 20% variations in terms of failure load and displacement, respectively. However, looking at the doped configurations, these presented smaller variations of about 2% and 10% for each respective variable. In all cases, by adding glass beads, crack initiation tended to change from adhesive to cohesive but with lower strength and ductility, correctly modeling the general experimental behavior as intended.

The Development and Study of a New Silylated Polyurethane-Based Flexible Adhesive-Part 2: Joint Testing and Numerical Modelling.

The need for more sustainable adhesive formulations has presented the possibility of using silane-based adhesives in the automotive industry. In this work, a dual-cure two-component silylated polyurethane resin (SPUR) adhesive was tested in single-lap joints, to assess in-joint behaviour at room temperature under quasi-static conditions for aluminium substrates. The effect of two different overlap lengths, 25 and 50 mm, was also considered. A numerical model was built using cohesive zone modelling in finite element software, to reproduce the mechanical behaviour of the joint. The model was fed with data experimentally withdrawn from the first part of this paper. A triangular-shaped cohesive zone model (CZM) law was chosen as the adhesive behaviour was highly elastic and lacked yielding phenomena. The experimental results served as the base for the numerical validation, allowing accurate CZM parameters to be successfully determined.

Characterization of Densified Pine Wood and a Zero-Thickness Bio-Based Adhesive for Eco-Friendly Structural Applications.

This study investigates a sustainable alternative for composites and adhesives in high-performance industries like civil and automotive. This study pioneers the development and application of a new methodology to characterize a bio-based, zero-thickness adhesive. This method facilitates precise measurements of the adhesive's strength and fracture properties under zero-thickness conditions. The research also encompasses the characterization of densified pine wood, an innovative wood product distinguished by enhanced mechanical properties, which is subsequently compared to natural pine wood. We conducted a comprehensive characterization of wood's strength properties, utilizing dogbone-shaped samples in the fiber direction, and block specimens in the transverse direction. Butt joints were employed for adhesive testing. Mode I fracture properties were determined via compact tension (CT) and double cantilever beam (DCB) tests for wood and adhesive, respectively, while mode II response was assessed through end-loaded split (ELS) tests. The densification procedure, encompassing chemical and mechanical processes, was a focal point of the study. Initially, wood was subjected to acid boiling to remove the wood matrix, followed by the application of pressure to enhance density. As a result, wood density increased by approximately 100 percent, accompanied by substantial improvements in strength and fracture energy along the fiber direction by about 120 percent. However, it is worth noting that due to the delignification nature of the densification method, properties in the transverse direction, mainly reliant on the lignin matrix, exhibited compromises. Also introduced was an innovative technique to evaluate the bio-based adhesive, applied as a zero-thickness layer. The results from this method reveal promising mechanical properties, highlighting the bio-based adhesive's potential as an eco-friendly substitute for synthetic adhesives in the wood industry.

Enhancing Fatigue Life and Strength of Adhesively Bonded Composite Joints: A Comprehensive Review.

Adhesive bonding is widely seen as the most optimal method for joining composite materials, bringing significant benefits over mechanical joining, such as lower weight and reduced stress concentrations. Adhesively bonded composite joints find extensive applications where cyclic fatigue loading takes place, but this might ultimately lead to crack damage and safety issues. Consequently, it has become essential to study how these structures behave under fatigue loads and identify the remaining gaps in knowledge to give insights into new possibilities. The fatigue life of adhesively bonded composite joints is influenced by various parameters, including joint configuration and material properties of adherends and adhesive. Numerous studies with varying outcomes have been documented in the literature. However, due to the multitude of influential factors, deriving conclusive insights from these studies for practical design purposes has proven to be challenging. Hence, this review aims to address this challenge by discussing different methods to enhance the fatigue performance of adhesively bonded composite joints. Additionally, it provides a comprehensive overview of the existing literature on adhesively bonded composite joints under cyclic fatigue loading, focusing on three main aspects: Adherends modification, adhesive modification, and joint configurations. Since the effect of modifying the adhesive, adherends, and joint configurations on fatigue performance has not been comprehensively studied in the literature, this review aims to fill this gap by compiling and comparing the relevant experimental data. Furthermore, this review discusses the challenges and limitations associated with the methods that can be used to monitor the initiation and propagation of fatigue cracks.

Rheological and Mechanical Properties of an Acrylic PSA.

The adhesion of pressure-sensitive adhesives (PSAs) is a complex phenomenon that can be understood through the characterization of different properties, including viscoelastic, mechanical, and fracture properties. The aim of the present paper is to determine the viscoelastic behaviour of an acrylic PSA and place it in the viscoelastic window, as well as to determine the tensile strength of the material. Additionally, different numbers of stacked adhesive layers and two crosshead speeds were applied to characterize the tensile strength of the adhesive in the different conditions. Adding a new interface between layers showed a negative influence in the tensile strength, while a higher crosshead speed implied a considerable increase in the same value. Finally, double cantilever beam (DCB) fracture tests were performed, and the J-integral approach was used to evaluate the fracture energy throughout the tests. The substrate roughness, the number of stacked layers, and the thickness of the PSA proved to decrease the performance of the PSA in fracture tests. While tensile bulk tests in viscoelastic materials are not easily found in the literature, as well as DCB tests, for fracture characterization, the obtained results allowed for the characterization of those properties in an acrylic PSA.

Acute pancreatitis caused by Systemic Lupus Erythematosus activity: A case report and literature review.

A 32-year-old woman with systemic lupus erythematosus came to the rheumatology outpatient clinic reporting abdominal pain for a week, along with fever, arthralgias, myalgias, alopecia, asthenia and dyspnea on exertion over the last two months. She was hypotensive and tachycardic, requiring admission to the intensive care unit. She was diagnosed with lupus-related acute pancreatitis, an unusual complication occurring in less than 1% of cases. Most cases are mild and self-limited; however, severe and life-threatening events with multiple organ failure are possible. This article is a case report of lupus-related critical acute pancreatitis, and a literature review.

Mujer de 32 años con lupus eritematoso sistémico acude a consulta externa de reumatología por dolor abdominal de una semana de evolución, además de fiebre, artralgias, mialgias, alopecia, astenia y disnea de esfuerzo de 2 meses de evolución. También presentó hipotensión y taquicardia, por lo que requirió ingreso en la unidad de cuidados intensivos. Le diagnosticaron pancreatitis aguda relacionada con el lupus, que es una complicación inusual que ocurre en menos del 1% de los pacientes. La mayoría de los casos son leves y autolimitados, sin embargo, es posible que se presenten eventos graves y potencialmente mortales, con disfunción multiorgánica. Este artículo es un reporte de caso de una pancreatitis aguda crítica relacionada con lupus y una revisión de la literatura.

Light and pH responsive catanionic vesicles based on a chalcone/flavylium photoswitch for smart drug delivery: From molecular design to the controlled release of doxorubicin.

Spatially and temporally localized delivery is a promising strategy to circumvent adverse effects of traditional drug therapy such as drug toxicity and prolonged treatments. Stimuli-responsive colloidal nanocarriers can be crucial to attain such goals. Here, we develop a delivery system based on dual light and pH responsive vesicles having a cationic bis-quat gemini surfactant, 12-2-12, and a negatively charged amphiphilic chalcone, C4SCh. The premise is to exploit the chalcone/flavylium interconversion to elicit a morphological change of the vesicles leading to the controlled release of an encapsulated drug. First, the phase behavior of the catanionic system is studied and the desirable composition yielding stable unilamellar vesicles identified and selected for further studies. The solutions containing vesicles (Dh ≈ 200 nm, ζ-potential ≈ 80 mV) are in-depth characterized by light microscopy, cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and surface tension measurements. Upon subjecting the vesicles to UV irradiation (λ = 365 nm) at near neutral pH (≈ 6.0), no morphological effects are observed, yet when irradiation is coupled with pH = 3.0, the majority of the vesicles are disrupted into bilayer fragments. The anticancer drug doxorubicin (DOX) is successfully entrapped in the non-irradiated vesicles, yielding an encapsulation efficiency of ≈ 25% and a loading capacity of ≈ 3%. The release profile of the drug-loaded vesicles is then studied in vitro in four conditions: i) no stimuli (pH = 6.0); ii) irradiation, pH = 6.0; iii) no irradiation and adjusted pH = 3.0; iv) irradiation and adjusted pH = 3.0 Crucially, irradiation at pH = 3.0 leads to a sustained release of DOX to ca. 80% (within 4 h), whereas cases i) and ii) lead to only ≈ 25 % release and case iii) to 50% release but precipitation of the vesicles. Thus, our initial hypothesis is confirmed: we present a proof of concept delivery system where light and pH act as inputs of an AND logic gate mechanism for the controlled release of a relevant biomedical drug (output). This may prove useful if the irradiated nanocarriers meet acidified physiological environments such as tumors sites, endosomes or lysosomes.

Acute pancreatitis caused by Systemic Lupus Erythematosus activity: A case report and literature review / Pancreatitis aguda por actividad del lupus eritematoso sistémico: Reporte de caso y revisión de la literatura

A 32-year-old woman with systemic lupus erythematosus came to the rheumatology outpatient clinic reporting abdominal pain for a week, along with fever, arthralgias, myalgias, alopecia, asthenia and dyspnea on exertion over the last two months. She was hypotensive and tachycardic, requiring admission to the intensive care unit. She was diagnosed with lupus-related acute pancreatitis, an unusual complication occurring in less than 1% of cases. Most cases are mild and self-limited; however, severe and life-threatening events with multiple organ failure are possible. This article is a case report of lupus-related critical acute pancreatitis, and a literature review.

Mujer de 32 años con lupus eritematoso sistémico acude a consulta externa de reumatología por dolor abdominal de una semana de evolución, además de fiebre, artralgias, mialgias, alopecia, astenia y disnea de esfuerzo de 2 meses de evolución. También presentó hipotensión y taquicardia, por lo que requirió ingreso en la unidad de cuidados intensivos. Le diagnosticaron pancreatitis aguda relacionada con el lupus, que es una complicación inusual que ocurre en menos del 1% de los pacientes. La mayoría de los casos son leves y autolimitados, sin embargo, es posible que se presenten eventos graves y potencialmente mortales, con disfunción multiorgánica. Este artículo es un reporte de caso de una pancreatitis aguda crítica relacionada con lupus y una revisión de la literatura.

Study of Hybrid Composite Joints with Thin-Ply-Reinforced Adherends.

It has been demonstrated that a possible solution to reducing delamination in a unidirectional composite laminate lies in the replacement of conventional carbon-fibre-reinforced polymer layers with optimized thin-ply layers, thus creating hybrid laminates. This leads to an increase in the transverse tensile strength of the hybrid composite laminate. This study investigates the performance of a hybrid composite laminate reinforced by thin plies used as adherends in bonded single lap joints. Two different composites with the commercial references Texipreg HS 160 T700 and NTPT-TP415 were used as the conventional composite and thin-ply material, respectively. Three configurations were considered in this study: two reference single lap joints with a conventional composite or thin ply used as the adherends and a hybrid single lap. The joints were quasi-statically loaded and recorded with a high-speed camera, allowing for the determination of damage initiation sites. Numerical models of the joints were also created, allowing for a better understanding of the underlying failure mechanisms and the identification of the damage initiation sites. The results show a significant increase in tensile strength for the hybrid joints compared to the conventional ones as a result of changes in the damage initiation sites and the level of delamination present in the joint.

From High Strain Rates to Elevated Temperatures: Investigating Mixed-Mode Fracture Behaviour in a Polyurethane Adhesive.

The investigation of the behaviour of adhesive joints under high strain rates is an active area of research, primarily due to the widespread use of adhesives in various industries, including automotive manufacturing. Understanding how adhesives perform when subjected to high strain rates is crucial for designing vehicle structures. Additionally, it is particularly important to comprehend the behaviour of adhesive joints when exposed to elevated temperatures. Therefore, this study aims to analyse the impact of strain rate and temperature on the mixed-mode fracture characteristics of a polyurethane adhesive. To achieve this, mixed-mode bending tests were conducted on test specimens. These specimens were subjected to three different strain rates (0.2 mm/min, 200 mm/min, and 6000 mm/min) and tested at temperatures ranging from -30 °C to 60 °C. The crack size was measured using a compliance-based method during the tests. For temperatures above Tg, the maximum load supported by the specimen increased with an increasing loading rate. GI increased by a factor of 35 for an intermediate strain rate and 38 for a high strain rate from low temperature (-30 °C) to room temperature (23 °C). GII also increased for the same conditions by a factor of 25 and 95 times, respectively.

P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice.

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: Sepsis was induced in wild-type (WT), P2X7-/-, and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7-/- sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba-1) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7-/- sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1ß (IL-1ß), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target.