Proposed mechanism explaining the role of lower respiratory tract cytokines/chemokines during acute MERS-CoV infection 0.1: MERS-CoV; 2: Activated neutrophil; 3: Neutrophil degranulation; 4: ...Neutrophil extracellular trap (NET) formation.
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•MERS-CoV infection downregulates Th1 and Th2 cytokines and chemokines.•MERS-CoV infection provokes high levels of IL-1α, IL-1β and IL-8 (CXCL8).•Inflammatory cytokines/chemokines correlate with MERS-CoV case fatality rate.•Th1/Th2 downregulation may contribute to severe infection and evolution of ARDS.
MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.
Recycled construction cementitious materials (RCCM) and red mud (RM) could be considered a type of discarded material with potential cementitious properties. Generally, landfilling and stacking are ...utilized to dispose of this type of solid waste, which can be detrimental to the environment and sustainability of the construction sector. Accordingly, a productive process for making eco-efficient alkali-activated slag-based samples with the inclusion of RCCM and red mud is studied in this paper. Dehydrated cement powder (DCP) is attained through the high-temperature treatment of RCCM, and red mud can be obtained from the alumina industry. Subsequently, DCP and RM are utilized as a partial substitute for granulated blast furnace slag (GBFS) in alkali-activated mixtures. Two different batches were designed; the first batch had only DCP at a dosage of 15%, 30%, 45%, and 60% as a partial substitute for GBFS, and the second batch had both DCP and RM at 15%, 30%, 45%, and 60% as a partial substitute for GBFS. Different strength and durability characteristics were assessed. The findings show that when both dehydrated cement powder and red mud are utilized in high quantities, the strength and durability of the specimens were enhanced, with compressive strength improving by 42.2% at 28 days. Such improvement was obtained when 7.5% each of DCP and RM were added. The results revealed that DCP and RM have a negative effect on workability, whilst they had a positive impact on the drying shrinkage as well as the mechanical strength. X-ray diffraction and micro-structural analysis showed that when the amount of DCP and RM is increased, a smaller number of reactive products forms, and the microstructure was denser than in the case of the samples made with DCP alone. It was also confirmed that when DCP and RM are used at optimized dosages, they can be a potential sustainable binder substitute; thus, valorizing wastes and inhibiting their negative environmental footprint.
Excessive use of natural resources and environmental concerns are key issues motivating the recycling of waste materials in the construction industry to minimize landfill problems. Free cement ...binders such alkali-activated binders have emerged as a prospective alternative to ordinary Portland cement, wherein diverse industrial, agriculture, and by-product waste materials have been converted as valuable spin-offs. Annually, tens of millions tons of red brick wastes are generated, which leads to several environmental problems. Thus, waste red brick powder (WRBP) was used as binder or a fine aggregate (silica sand) substitute to prepare some new types of alkali-activated mortars (AAMs). These mortars contained ground blast furnace slag (GGBFS) and metakaolin (MK) with various levels of WRBP (0, 15, 30, and 45%) as a substitute for silica sand. The prepared AAMs were cured at 300 °C, 600 °C, and ambient temperature. All the specimens were tested to determine the effects of various WRBP contents on the workability, strengths, and microstructures of the designed AAMs. The workability of the fresh AAMs was considerably dropped due to the incorporation of WRBP as binary binder or fine aggregate replacement. In addition, AAM containing 15% of WRBP as GGBFS and MK replacement displayed a significant improvement (by 30.7%) in the strength performance. However, the increasing content of WRBP to 30% and 45% significantly led to a decrease in compressive strength from 49.9 MPa to 44.7 and 34.2 MPa, respectively. Overall, the mortars’ strength was increased with the increase in WRBP contents from 0 to 45% as sand substitute. Conversely, the mortars strength was reduced with the increase in curing temperatures. The microstructure analyses of the studied mortars revealed an appreciable enhancement of the geopolymerization process, gels formulation, and surface morphology, leading to an improvement in their compressive and flexural strength characteristics. It was asserted that high-performance mortars with customized engineering properties can be designed via the inclusion of WRBP into alkali-activated MK-GGBFS mixes.
The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, ...tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.
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Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by Klebsiella pneumoniae are ...notorious for being difficult to treat due to resistance to commonly used antimicrobials. Klebsiella pneumoniae isolates from bloodstream infections are becoming increasingly resistant to carbapenems. In the fight against carbapenem-resistant Klebsiella pneumoniae, colistin polymyxin E is the antimicrobial of choice and is thus widely used. Objective: This study aimed to determine the global prevalence of colistin resistance amongst Klebsiella pneumoniae isolates from bloodstream infections. Methods: PubMed, Medline, Scopus, and the Cochrane Library were searched for published articles without restricting the search period. Studies meeting the predefined inclusion and exclusion criteria were included, and quality was assessed using Joanna Briggs Institute Checklist. We used a statistical random effect model to analyze data with substantial heterogeneity (I2 > 50%) in the meta-analysis. Results: A total of 10 studies out of 2873 search results that met the inclusion criteria were included in the final synthesis for this study. A pooled prevalence of colistin resistance was 3.1%, 95% CI (1.5−4.7%). The highest colistin resistance pooled prevalence was recorded in isolates studied in 2020 and beyond 12.90% (4/31), while Klebsiella pneumoniae isolates studied in 2015 and before and in 2016−2019 showed a pooled colistin resistance rate of 2.89% (48/1661) and 2.95% (28/948), respectively. The highest colistin resistance was found in Klebsiella pneumoniae isolates from Thailand (19.2%), while the least pooled resistance was in Klebsiella pneumoniae from South Korea (0.8%). The pooled prevalence of the multidrug-resistant (MDR) of Klebsiella pneumoniae from bloodstream infection ranged from 80.1%, 95% CI (65.0−95.2%), and the resistance prevalence of other antibiotics by Klebsiella pneumoniae from bloodstream infections were as follows; ciprofloxacin (45.3%), ertapenem (44.4%), meropenem (36.1%), imipenem (35.2%), gentamicin (33.3%), amikacin (25.4%) and tigecycline (5.1%). Klebsiella pneumoniae recovered from the intensive care unit (ICU) showed higher colistin resistance, 11.5% (9/781%), while non-ICU patients showed 3.03% (80/2604) pooled colistin resistance. Conclusion: This study showed low colistin resistance in Klebsiella pneumoniae isolates from global bloodstream infections. However, significant colistin resistance was observed in isolates collected from 2020 and beyond. Significant colistin resistance was also observed in Klebsiella pneumoniae isolates in bloodstream infections from the intensive care unit (ICU) compared to those from non-ICUs. As a result, there is a need to institute colistin administration stewardship in the ICU in clinical settings.
Abnormal loads can produce localized damage that can eventually cause progressive collapse of the whole reinforced concrete (RC) structure. This might have devastating financial repercussions and ...cause numerous severe casualties. Numerical simulation, using the finite element method (FEM), of the consequences of abnormal loads on buildings is thus required to avoid the significant expenses associated with testing full-scale buildings and to save time. In this paper, FEM simulations, using ABAQUS software, were employed to investigate the progressive collapse resistance of the full-scale three-dimensional (3D) beam–slab substructures, considering two concrete mixes, namely: normal concrete (NC) and rubberized concrete (RuC) which was made by incorporating crumb rubber at 20% by volume replacement for sand. The FEM accuracy and dependability were validated using available experimental test results. Concrete and steel material non-linearity were considered in the FE modelling. The numerical study is extended to include eight new models with various specifics (a set of parameters) for further understanding of progressive collapse. Results showed that slabs contribute more than a third of the load resistance, which also significantly improves the building’s progressive collapse resistance. Moreover, the performance of the RuC specimens was excellent in the catenary stage, which develops additional resilience to significant deformation to prevent or even mitigate progressive collapse.
Green concrete is a sustainable composite material having natural and waste materials replacing carbon dioxide gas-producing cement, and aggregates in the concrete. Thus, it significantly contributes ...in reducing greenhouse gas emissions and improves the economic viability of a country as well. Literature suggests that research on the development of green concrete is evolving with widely-available natural and waste materials. Considering the need for the development of green concrete, the current research is conducted. It was hypothesized that the mechanical performance of green concrete prepared by substituting cement with Natural Zeolite (NZ) and waste Polyethylene Terephthalate (PET) fibers will yield stronger, cost-effective, and environmentally green concrete for the construction industry. The microstructure, morphology, and surface properties of the locally extracted NZ were characterized using X-ray Diffraction, SEM and BET, respectively. The influence of quantity, shape, orientations, and surface of NZ and PET fibers along with varying curing times, i.e., 28, 90, and 180 days were considered for experimentation. The main findings of this study are that two optimum proportions for the concrete mixtures are obtained: the first one was 10 % NZ while the other one was 2.5 % PET, and 15 % NZ, and 1.0 % PET. These optimum mixing ratios were found to enhance the compressive strength of concrete, reduce the production cost, and reuse waste PET bottles effectively, which are key points of this study. Furthermore, the workability of the fresh concrete was improved with higher proportions of PET rather than NZ. Finally, the findings of the current research highlight a pragmatic remedial solution for saving energy, turning non-decomposable waste into useful materials for green concrete, and simultaneously contributing to a cleaner environment.
Sialic acid that presents on the surface of lung epithelial cells is considered as one of the main binding targets for many respiratory viruses, including influenza and the current coronavirus ...(SARS-CoV-2) through the viral surface protein hemagglutinin. Gold nanoparticles (Au NPs) are extensively used in the diagnostic field owing to a phenomenon known as 'surface plasmonic resonance' in which the scattered light is absorbed by these NPs and can be detected via UV-Vis spectrophotometry. Consequently, sialic acid conjugated Au NPs (SA-Au NPs) were utilized for their plasmonic effect against SARS-CoV-2, influenza B virus, and Middle-East respiratory syndrome-related coronavirus (MERS) in patients' swab samples. The SA-Au NPs system was prepared by a one-pot synthesis method, through which the NPs solution color changed from pale yellow to dark red wine color, indicting its successful preparation. In addition, the SA-Au NPs had an average particle size of 30 ± 1 nm, negative zeta potential (-30 ± 0.3 mV), and a UV absorbance of 525 nm. These NPs have proven their ability to change the color of the NPs solutions and patients' swabs that contain SARS-CoV-2, influenza B, and MERS viruses, suggesting a rapid and straightforward detection tool that would reduce the spread of these viral infections and accelerate the therapeutic intervention.
When COVID-19 was first announced back in 2019, there were vast number of attempts to halt the progression of the SARS-CoV-2 virus once and for all ...
Monkeypox virus has remained the most virulent poxvirus since the elimination of smallpox approximately 41 years ago, with distribution mostly in Central and West Africa. Monkeypox (Mpox) in humans ...is a zoonotically transferred disease that results in a smallpox-like disease. It was first diagnosed in 1970 in the Democratic Republic of the Congo (DRC), and the disease has spread over West and Central Africa. The purpose of this review was to give an up-to-date, thorough, and timely overview on the genomic diversity and evolution of a re-emerging infectious disease. The genetic profile of Mpox may also be helpful in targeting new therapeutic options based on genes, mutations, and phylogeny. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of Mpox cases are critical tools for obtaining a better knowledge of the ever-changing epidemiology of this disease.
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