Search

Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females.We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates.Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD.Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females.

The hepatitis B and C viruses persist by evasion of T cell immunity. Persistence depends upon premature failure of CD4+ T cell help and loss of CD8+ T cell control because of epitope mutational escape and/or functional exhaustion. Powerful new immunological and transcriptomic tools provide insight into the mechanisms of T cell silencing by HBV and HCV. Similarities are apparent, including dysregulated expression of common inhibitory/immune checkpoint receptors and transcription factors. There are also differences. T cell exhaustion is uniform in HCV infection, but varies in HBV infection depending on disease stage and/or protein target. Here, we review recent advances defining similarities and differences in T cell evasion by HBV and HCV, and the potential for reversal following antiviral therapy.

This research investigated the reuse potential of pomegranate peels waste (PPW) in the production of fired clay bricks with improved thermo-physical and mechanical properties. PPW was used as a substitute for natural clay with different replacement ratios ranging from 0 to 12.5% with a stride of 2.5 wt%. The impact of adding PPW on compressive strength, total porosity, water absorption, bulk density, thermal conductivity and microstructure characteristics has been assessed for bricks fired at 900, 1000 and 1100 °C. With the increase of PPW replacement ratio, the bulk density, thermal conductivity and compressive strength decreased. The obtained results confirm the possibility of using PPW as a sustainable pore forming agent in brick industry. The incorporation of 12.5 wt% PPW showed the lowest bulk density (1230 kg/m3), the lowest thermal conductivity (0.2 W/mK), the lowest compressive strength (5.5 MPa), the highest water absorption (38%), and the highest total porosity (48%) for bricks fired at 1000 °C. The obtained compressive strength satisfies the minimum acceptable requirements for clay bricks. The contribution of the newly developed bricks to the energy consumption performance of a building model has been evaluated by using DesignBuilder energy simulation software. A considerable reduction in the annual energy consumption by about 23.3% has been attained as compared to the traditional bricks.

Hepatitis C virus (HCV) infection resolves spontaneously in ∼25% of acutely infected humans where viral clearance is mediated primarily by virus-specific CD8+ T cells. Previous cross-sectional analysis of the CD8+ TCR repertoire targeting two immunodominant HCV epitopes reported widespread use of public TCRs shared by different subjects, irrespective of infection outcome. However, little is known about the evolution of the public TCR repertoire during acute HCV and whether cross-reactivity to other Ags can influence infectious outcome. In this article, we analyzed the CD8+ TCR repertoire specific to the immunodominant and cross-reactive HLA-A2–restricted nonstructural 3-1073 epitope during acute HCV in humans progressing to either spontaneous resolution or chronic infection and at ∼1 y after viral clearance. TCR repertoire diversity was comparable among all groups with preferential usage of the TCR-β V04 and V06 gene families. We identified a set of 13 public clonotypes in HCV-infected humans independent of infection outcome. Six public clonotypes used the V04 gene family. Several public clonotypes were long-lived in resolvers and expanded on reinfection. By mining publicly available data, we identified several low-frequency CDR3 sequences in the HCV-specific repertoire matching human TCRs specific for other HLA-A2–restricted epitopes from melanoma, CMV, influenza A, EBV, and yellow fever viruses, but they were of low frequency and limited cross-reactivity. In conclusion, we identified 13 new public human CD8+ TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of cross-reactive TCRs suggests that they are not major determinants of infectious outcome.

The partial substitution of ordinary Portland Cement (OPC) with clay minerals as supplementary cementitious materials has been currently considered as an effective approach for reducing the harmful environmental impact and health risks of OPC. Although cement mortars are not easily ignitable, the exposure to elevated temperatures can alter their microstructure, leading to reduction in the strength and damage. Therefore, improving the temperature resistance of the cement mortars through the incorporation of local clay minerals has been proposed in this study. The mechanical performance and physical properties of cement mortars containing Wasia Formation clay (WFC) exposed to 700 °C have been investigated. OPC was partially replaced with WFC at various mass ratios of 0, 5, 10, 15, and 20 wt%. Several methods were used to assess the physico-mechanical and structural properties such as compressive strength testing, ultrasonic pulse velocity (UPV), Schmidt hamme, scanning electron microscopy, and X-ray powder diffraction (XRD). The addition of WFC as partial replacement of the cement showed a significant enhancement in the compressive strength for the mortars exposed to normal and elevated temperatures. The compressive strength of the mortar incorporating 20 wt% of WFC and exposed to 700 °C is about 2.5-fold greater than that of the ordinary mortar. Even after exposure to 700 °C, the UPV for the 20 wt% WFC-blended mortar is 30% greater than that for ordinary mortar, indicating the improved structural integrity of the blended mortars. The WFC-blended mortars showed dense and compact microstructure confirming the improvement in the strength of mortars.

In this work, an eco-friendly lightweight cementless mortar has been prepared primarily from natural resources and industrial solid wastes. Lime–silica fume (lime–SF) paste (1 : 1 wt) was used as a green binder in lieu of cement. The binder was combined with expanded perlite (EP) aggregate with various aggregate volume contents of 25, 50 and 75%. The compressive strength, indirect tensile strength, bulk density, thermal conductivity, thermal diffusivity and solar reflectivity of the hardened mortars were determined at 28 d of curing. Thermogravimetric analysis (TGA) was used to assess the phase composition. The durability of the developed mortars was estimated with an accelerated aging test. The results showed that the newly developed mortar possesses reasonable mechanical performance, reduced thermal conductivity and enhanced solar reflectivity. The increased porosity of EP-blended mortar facilitates water migration within the hardened structure, leading to remarkable enhancement in resistance to wetting/drying aging conditions and hence improved durability. TGA patterns revealed a phase composition similar to that of the hydrated cement. Scanning electron microscopy showed that good bonding exists between the hardened lime–pozzolan matrix and EP aggregate. The lightweight mortar developed can be highly recommended for plastering and rendering applications in sustainable and energy-efficient buildings.

Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system.

Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.

The improvement in the physico-mechanical properties of lime–silica fume (SF) pastes through the incorporation of nano-metakaolin (NMK) was investigated. Lime–SF paste (1 : 1 by weight) was prepared as a reference binder. To examine the influence of NMK on strength development, SF was replaced with 2–10 wt% NMK. The compressive strength, capillary water absorption and pore structure of the designed mixes were determined after 3, 7 and 28 d of curing. X-ray diffraction analysis and differential scanning calorimetry were used to study the phase composition and scanning electron microscopy (SEM) was used for microstructural investigations. The lime–SF binder modified with 6% NMK exhibited the best mechanical performance. Pore structure analysis confirmed that NMK provided significant refinement in the pore structure of the blended pastes and SEM micrographs revealed noticeable microstructural improvements. The capillary water absorption coefficient decreased considerably with an increase in NMK content up to 6% compared with the reference mixture. Use of the developed lime–SF–NMK paste is recommended as a promising innovative binder for specific cement applications such as plastering and renovation of buildings.

This study investigates the mechanical and thermal properties of cement mortars incorporating two types of waste slags: ferrochrome (FeCr) slag aggregate was used as a replacement for sand at ratios of 25, 50, 75 and 100 wt%, and ground granulated blast furnace slag (GGBS) was used as a partial replacement for cement at a ratio of 25 wt%. Compressive strength, volume of permeable voids (VPV), drying shrinkage, and thermal conductivity tests were conducted after 28 days of curing. The microstructure characteristics were examined by scanning electron microscopy. The experimental results revealed that FeCr waste aggregates could satisfactorily replace natural fine sand in cement mortars up to 25 wt% without a remarkable degradation of compressive strength. Furthermore, increasing the replacement ratios of FeCr aggregates by over 25 wt% resulted in a noticeable decrease in thermal conductivity and an increase in the permeable void content of cement mortars. The increased VPV of FeCr slag-blended mortars led to a significant increase in drying shrinkage. The integration of GGBS with FeCr aggregates led to enhanced compressive strength and reduced VPV and drying shrinkage, thus contributing to an improved microstructure.

Response to immune checkpoint blockade cancer immunotherapy is variable, but the mechanisms that underlie this variability remain unclear. In a recent issue of Nature Medicine, Yu et al. demonstrate that liver metastases limit immunotherapy efficacy by promoting macrophage-mediated elimination of tumor-specific CD8+ T cells. Liver-directed radiotherapy in preclinical models could partially overcome this effect.

Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic.

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

Interactions between the host immune system and the viral variants determine persistence of hepatitis C virus (HCV) infection after the acute phase of infection. This study describes the genetic variability of within-host HCV viral variants in acute infection and correlates it with host and virus-related traits and infection outcome. Next generation sequence data (Illumina, MiSeq platform) of viral genomes from 116 incident acute infections (within 180 days of infection) were analysed to determine all the single nucleotide polymorphism (SNP) frequencies above a threshold of 0.1%. The variability of the SNPs for the full open reading frame of the genome as well as for each protein coding region were compared using mean standardised Shannon Entropy (SEs) values calculated separately for synonymous and non-synonymous mutations. The envelope glycoproteins regions (E1 and E2) had the highest SE values (indicating greater variability) followed by the NS5B region. Non-synonymous mutations rather than synonymous mutations were the main contributors to genomic variability in acute infection. The mean difference of Shannon Entropy was also compared between subjects after categorizing the samples according to host and virus-related traits. Host IFNL3 allele CC polymorphism at rs12979860 (vs. others) and viral genotype 1a (vs. 3a) were associated with higher genomic variability across the viral open reading frame. Time since infection, host gender or continent of origin were not associated with the viral genomic variability. Viral genomic variability did not predict spontaneous clearance.

Cement manufacturing, which is partially responsible for environmental and health risks as well as the greenhouse gas emissions, is a binder industry that needs energy and raw material. To decrease the needing, this study develops nano-modified eco-friendly cementitious composites including industrial solid wastes and/or by-products. For this purpose, ordinary Portland cement (OPC) was partially replaced with 70 wt% of fly ash (FA), Nano metakaolin (NMK) was incorporated at a rate of 2, 4, 6, 8, 10, 12 and 14 % as partial replacement by weight of FA to take advantage of the great role of nano materials in improving the mechanical and physical properties of cement based materials. Compressive strength, flexural strength, and capillary water absorption coefficient have been studied at 28 days of curing according to the international ASTM standards. Differential scanning calorimeter (DSC) was used to study the phase composition/decomposition. The microstructure characteristics of the hardened samples were investigated by scanning electron microscope (SEM) equipped with energy dispersive analytical x-ray unit (EDAX). The results revealed that the partial replacement of cement by 70% of FA has reduced both compressive and flexural strengths by about 45% in addition; the water absorption has been increased by about 175% as compared to the OPC. The replacement of FA by different amounts of NMK compensate for the loss in strength by about 75%. Furthermore, NMK has considerably improved the microstructure and reduced the water absorption by 86%. The study concluded that, it is possible to substitute 70% of the weight of the cement in the production of eco-friendly cementitious composites with improved mechanical performance attaining 88% of the corresponding performance of the hydrated OPC. The developed composites can be considered as green binders and recommended for various applications in construction industry.

Hepatitis C virus (HCV) infection resolves spontaneously in approximately 25% of acutely infected humans where viral clearance is mediated primarily by virus specific CD8+ T cells. Previous cross-sectional analysis of the CD8+ T cell receptor (TCR) repertoire targeting two immunodominant HCV epitopes reported widespread use of public TCRs shared by different subjects, irrespective of infection outcome. However, little is known about the evolution of the public TCR repertoire during acute HCV and whether cross-reactivity to other antigens can influence infectious outcome. Here, we analyzed the CD8+ TCR repertoire specific to the immunodominant and cross-reactive HLA-A2 restricted NS3-1073 epitope during acute HCV in humans progressing to either spontaneous resolution or chronic infection, and at ~1-year following viral clearance. TCR repertoire diversity was comparable among all groups with preferential usage of the T cells receptor beta V04 and V06 gene families. We identified a set of thirteen public clonotypes in HCV-infected humans independent of infection outcome. Six public clonotypes used the V04 gene family. Several public clonotypes were long-lived in resolvers and expanded upon reinfection. By mining publicly available data, we identified several low frequency CDR3 sequences in the HCV-specific repertoire matching human TCRs specific for other HLA-A2 restricted epitopes from melanoma, cytomegalovirus, influenza A, Epstein-Barr and yellow fever viruses but they were of low frequency and limited cross-reactivity. In conclusion, we identified thirteen new public human CD8+ TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of cross-reactive TCRs suggest that they are not major determinants of infectious outcome.

To evaluate the influence of airborne particle abrasion, Piranha acid and hot acid etching on bond strength of zirconia with self-adhesive resin cements after aging. Also, the effect of Silano-Pen treatment on the bond strength of zirconia to resin cements.Thirty-six zirconia blocks were cut, sintered and divided into three groups (n=12); Airborne particle abrasion, Piranha acid, and hot acid etching were then treated with Silano-Pen. Each zirconia block was bonded to its corresponding composite block utilizing either Panavia SA, TheraCem or Panavia F2.0. 360 micro -tensile test bars were obtained and half of them were subjected to 10000 thermal aging cycles. Each microtensile test bar was subjected to microtensile force until debonding. Scanning Electron Microscopic evaluation was performed.There was a significant difference between the surface treatments. Hot acid showed the highest mean bond strength and the lowest was Piranha acid. Panavia SA significantly improved the bond strength compared to TheraCem and Panavia F2.0. The interaction between cement and Silano-Pen was non-significant (p=.067). Under SEM analysis, hot acid treatments showed homogenous granular texture with wide distribution of porous network.Pre-treatment, resin cement, and aging influences the effectiveness of bonding of zirconia. Silano-Pen after hot acid improved the bonding of zirconia.

Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.

The engagement of activating NK receptors (aNKR) stimulates NK cell activity, provided that interactions between inhibitory NK receptors (iNKR) with their HLA ligands do not override them. Abs bound to target cells can also activate NK cells by engaging the CD16 aNKR. NK cell education status is an important factor for Ab‐dependent NK cell activation (ADNKA) of some NK cell subsets. However, whether NK cell education also influences Ab‐dependent cellular cytotoxicity (ADCC) levels is not fully known. ADCC‐GranToxiLux (GTL) assays measured ADCC activity as the frequency of granzyme B positive (%GzB+) target cells. Target cells were anti‐HIV Immunoglobulin G (HIVIG)‐opsonized CEM‐NKr.CCR5 (CEM) cells. Lymphocytes and sorted single positive (SP) NKG2A+, KIR2DL1+, KIR2DL3+, and KIR3DL1+ NK cells, to self‐ and nonself HLA, were used as effectors in ADCC‐GTL assays to examine how education status influenced ADCC activity. ADNKA activity was assessed by stimulating lymphocytes with HIVIG‐opsonized CEMs and measuring the frequency of NK cell populations defined by their expression of iNKRs, along with IFN‐γ, CCL4, and CD107a functions. ADCC: the %GzB+ CEM cells generated by self‐ versus nonself HLA‐specific SPiNKR did not differ. ADNKA: More NK cells educated through KIR2DL1 and KIR3DL1, but not KIR2DL3, responded to ADNKA than their uneducated counterparts. CD16 engagement induced ADCC and ADNKA activity. With the proviso that groups’ sizes were small, our results support the notion that NK cell education does not influence ADCC levels but does contribute to ADNKA activity., NK cell education through inhibitory Killer Immunoglobulin‐like Receptors activates antibody‐dependent NK cell functions but mediate antibody‐dependent cellular cytotocitiy no better than their uneducated counterparts.

The immune landscape of the tumor microenvironment (TME) is a determining factor in cancer progression and response to therapy. Specifically, the density and the location of immune cells in the TME have important diagnostic and prognostic values. Multiomic profiling of the TME has exponentially increased our understanding of the numerous cellular and molecular networks regulating tumor initiation and progression. However, these techniques do not provide information about the spatial organization of cells or cell-cell interactions. Affordable, accessible, and easy to execute multiplexing techniques that allow spatial resolution of immune cells in tissue sections are needed to complement single cell-based high-throughput technologies. Here, we describe a strategy that integrates serial imaging, sequential labeling, and image alignment to generate virtual multiparameter slides of whole tissue sections. Virtual slides are subsequently analyzed in an automated fashion using user-defined protocols that enable identification, quantification, and mapping of cell populations of interest. The image analysis is done, in this case using the analysis modules Tissuealign, Author, and HISTOmap. We present an example where we applied this strategy successfully to one clinical specimen, maximizing the information that can be obtained from limited tissue samples and providing an unbiased view of the TME in the entire tissue section.

This study investigates the effect of nano metakaolin (NMK) on the thermo-physical, mechanical and microstructural properties of hardened cement mortar containing high amount of ferrochrome (FeCr) slag. Sand was replaced with FeCr-slag aggregate at the ratio of 50 mass, %. Cement was partially replaced with different amounts of NMK at the ratios of 2, 4, 6, 8, 10, 12 and 14 mass, %. Compressive strength, flexural strength, drying shrinkage, capillary water absorption and thermal conductivity of the hardened nano-modified mortars were determined in accordance with ASTM standards at 28 days of water curing. The microstructure characteristics of the hardened samples were investigated by scanning electron microscope (SEM) equipped with energy dispersive analytical X-ray unit (EDAX). The results showed considerable improvements in the mechanical and thermal performance of cement mortar, due to the incorporation of FeCr-slag; in addition, the replacement of cement by NMK was found to be effective in providing an additional enhancement in the mechanical strength and thermal conductivity. Furthermore, NMK containing mortar has considerably reduced drying shrinkage and capillary water absorption. The reduction in drying shrinkage for the mortar containing 50 mass, % FeCr-slag and modified with 10 mass, % NMK reached 87% relative to the reference mortar. The microstructure of the hardened mortar containing NMK appeared quite dense and compact with finer pore structure.

The use of nano materials as partial replacement for cement has been considered all over the world, particularly in the production of high strength and high performance cement based structures. This study aims at facile production of nano-scale metakaolin (NMK) and investigating its influence on the mechanical, pore structure, phase composition and microstructure characteristics of hardened mortar. NMK with superior surface area was effortlessly prepared via exfoliation of thermally activated ordinary kaolin (MK) with the aid of organic ammonium chloride. SEM micrographs confirm the formation of nanoplates of few nanometers in thickness; furthermore, specific surface area was evaluated by the BET analysis. The exfoliated NMK showed greatly enhanced surface area. Two groups of MK-blended mortars were prepared in which cement was partially replaced with 0, 1, 2, 3, 4, and 5 wt% of MK and Exfoliated NMK. Exfoliated NMK was found to be highly effective in enhancing the compressive strength of mortar and an optimum replacement within 3% can be concluded. There were enhancements by about 24% compared with the unexfoliated MK blended mortar and 54% compared with the plain ordinary mortar. The BET analysis confirmed that; NMK provides significant refinement in pore structure of blended mortar. The phase composition analysis by TGA and SEM indicate that NMK acts not only as a filler to improve the packing inside the cementitious matrix, but also as an activator to promote hydration and pozzolanic reactions.

In this work, we report the simple, low temperature and rapid microwave-assisted synthesis of undoped and Gadolinium (III) doped lead iodide with different morphologies, i.e. nanorods of average diameter ~200 nm and hierarchical (flower-shaped) nanosheets of thicknesses less than 100 nm. Prepared nanostructures were typify in details using a variety of analytical techniques that reveal the well crystallinity with hexagonal structure. We found that by changing the concentrations of Gadolinium (III) one can tailor the size and shape of nanostructures of lead iodide. The presence of Gadolinium (III) doping was assessed by energy dispersive X-ray analysis. Optical band gap and Photoluminescence intensity are found to be enhanced due to Gadolinium (III) doping. The value of Gamma linear absorption coefficient is found to be enriched with doping, which suggests its application in radiation detection.

Owing to the growing environmental pressure to reduce waste and pollution, the effective utilization of industrial solid wastes in construction applications has gained notable attention. This study investigates the mechanical and thermal properties of cement mortars incorporating two types of waste slags. Ferrochrome (FeCr) slag aggregate was used as a replacement for sand at the ratios of 25, 50, 75 and 100 wt. %. Ground granulated blast furnace slag (GGBS) has been used as a partial replacement of cement at the ratio of 25 wt. %. Compressive strength, permeable voids content and thermal conductivity tests have been conducted after 28 days of curing. The microstructure characteristics have been investigated by scanning electron microscope (SEM) equipped with energy dispersive analytical x-ray unit (EDAX). The experimental results revealed that FeCr waste aggregates could satisfactorily replace for natural fine sand in cement mortars up to 25 wt. % without a remarkable degradation of the compressive strength. Furthermore, Increasing replacement ratios of FeCr aggregates over 25 wt. % have resulted in noticeable decrease in thermal conductivity and an increase in the permeable voids content of cement mortars. The integration of GGBS with FeCr aggregates leads to enhanced compressive strength, reduced voids content and contribute to improved microstructure. The developed mortars with comparatively improved thermal resistance can be recommended for several structural and non-structural applications especially in hot weather regions. The authors would like to acknowledge the financial support provided by Sohar Port and Free Zone Company under Sultan Qaboos University Grant No. CR/ENG/ CAED/18/07.

Hepatitis C virus (HCV) affects approximately 250,000 Canadians. Although safe and effective (>95% cure rates) antiviral therapies have become available within the past 5 years, chronic HCV infection still remains a major driver of end-stage liver disease and liver transplantation. Both the Canadian Institute for Health Research and the Public Health Agency of Canada recognize the impact of HCV-related liver diseases and support the Canadian Network for Hepatitis C (CanHepC), a National network for the scientific study of hepatitis C that organizes an annual symposium as part of its knowledge translation mandate. At the 8th Canadian Symposium on Hepatitis C Virus in May 2019, basic scientists, clinicians, epidemiologists, social scientists, and community members came together to share their work under the theme of “Improving diagnosis and linkage to care”. This symposium also marked the launch of the Blueprint to inform hepatitis C elimination efforts in Canada, a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial and federal organizations developing their own HCV elimination strategies.

This study aims to examine the potential of natural clay mineral from the southern part of Saudi Arabia as an effective adsorbent material for the removal of heavy metal ions of cadmium (Cd) and nickel (Ni) from aqueous solutions. The SEM analysis showed that clay particles had mixed shapes such as elongated rod-like and rectangular shape having rough corners with larger particles of 2-8 µm in size and smaller particles in the sub-micron size range. X-ray diffraction data revealed that clay particles had a good crystalline structure and composed of a mixture of various minerals including feldspar, illite, quartz, calcite, and gypsum. The BET surface area was found to be 35 ± 1 m ² /g and the average pore size and pore volume of 6.5 ± 0.5 nm and 5.7e-02 cc/g, respectively. The X-ray fluorescence analysis of clay showed main compounds of SiO₂ (47.33%), Al₂O₃ (18.14%), Fe₂O₃ (15.89%) with many others such as CaO, MgO, TiO₂, and K₂O in minor quantities. It was found that 1.2 g of clay removed up to 99.5% of Ni and 97.5% of Cd from 40 ppm aqueous solutions. The metal removal efficiencies were increased from around 95% up to 99% by increasing the pH of aqueous solutions from 4 to 11. The adsorption of Ni and Cd ions on Saudi clay was relatively fast, and up to 97% of ions were removed from solution within 45 min. The SEM-EDX and BET analysis for recycled clays further confirmed that the metal ions were removed from water through adsorption onto the clay. The experimental data fitted well with Langmuir and Freundlich isotherms. The maximum adsorption capacity of clay for Cd and Ni from isotherms was found to be 3.3 and 2.7 mg/g respectively. The findings of this study confirm the potential role of Saudi natural clay in wastewater treatment processes as a cheap, environment-friendly and safe natural adsorbent material.

Transfer of hepatitis C virus (HCV) infection from a donor to a new recipient is associated with a bottleneck of genetic diversity in the transmitted viral variants. Existing data suggests that one, or very few, variants emerge from this bottleneck to establish the infection (transmitted founder [T/F] variants). In HCV, very few T/F variants have been characterized due to the challenges of obtaining early infection samples and of high throughput viral genome sequencing. This study used a large, acute HCV, deep-sequenced dataset from first viremia samples collected in nine prospective cohorts across four countries, to estimate the prevalence of single T/F viruses, and to identify host and virus-related factors associated with infections initiated by a single T/F variant. The short reads generated by Illumina sequencing were used to reconstruct viral haplotypes with two haplotype reconstruction algorithms. The haplotypes were examined for random mutations (Poisson distribution) and a star-like phylogeny to identify T/F viruses. The findings were cross-validated by haplotype reconstructions across three regions of the genome (Core-E2, NS3, NS5A) to minimize the possibility of spurious overestimation of single T/F variants. Of 190 acute infection samples examined, 54 were very early acute infections (HCV antibody negative, RNA positive), and single transmitted founders were identified in 14 (26%, 95% CI: 16–39%) after cross validation across multiple regions of the genome with two haplotype reconstruction algorithms. The presence of a single T/F virus was not associated with any host or virus-related factors, notably viral genotype or spontaneous clearance. In conclusion, approximately one in four new HCV infections originates from a single T/F virus. Resolution of genomic sequences of single T/F variants is the first step in exploring unique properties of these variants in the infection of host hepatocytes.

Background While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. Methods Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex‐specific analyses. Results Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1–20.7) in females and 7.6/100 PYO (95% CI, 6.0–9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37–2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25–2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62–4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01–2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33–1.53]; P < .001). Conclusions Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naive patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (

Acute hepatitis C virus (HCV) infection culminates in viral persistence in the majority of cases. Abs that recognize the envelope glycoproteins E1 and E2 are generated during the late stages of acute infection, yet their contribution to spontaneous viral clearance remains controversial. Investigation of the humoral responses during acute HCV infection have been limited by the inability to directly identify and characterize HCV-specific B cells. In this study we describe the development of a novel tetramer of the E2 glycoprotein ectodomain (J6, genotype 2a strain), which allowed us to visualize E2-specific B cells longitudinally in the peripheral blood of HCV-infected individuals. HCV-specific class-switched memory B cells were detected in 3 out of 7 participants during late acute infection, with a mean frequency of 0.63% for positive samples (range 0.16–0.67%) and in 7 out of 7 participants with chronic infection with a mean frequency of 0.47% (range 0.20–0.78%). In a cross-sectional study, E2 tetramer positive population was detected in 28 out of 31 chronically infected individuals. Deep sequencing of the BCR from E2-specific class-switched memory B cells sorted from two independent participants revealed a focused repertoire suggestive of clonal selection. Tetramer-specific B cells exhibited skewed CDR3 length distribution and increased mutation frequency compared with naive B cells. This BCR profile is indicative of clonal expansion and affinity maturation. E2 tetramer allows for specific and sensitive ex vivo characterization of rare HCV-specific B cells in infected individuals, and will enable researchers to gain a better understanding of humoral immunity in HCV infection.

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC(3) ). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities

Background In Canada, interferon-free, direct-acting antiviral hepatitis C virus (HCV) regimens are costly. This presents challenges for universal drug coverage of the estimated 220 000 people with chronic HCV infection nationwide. The study objective was to appraise criteria for reimbursement of 4 HCV direct-acting antivirals in Canada. Methods We reviewed the reimbursement criteria for simeprevir, sofosbuvir, ledipasvir-sofosbuvir and paritaprevir-ritonavir-ombitasvir plus dasabuvir in the 10 provinces and 3 territories. Data were extracted from April 2015 to June 2016. The primary outcomes extracted from health ministerial websites were: 1) minimum fibrosis stage required, 2) drug and alcohol use restrictions, 3) HIV coinfection restrictions and 4) prescriber type restrictions. Results Overall, 85%-92% of provinces/territories limited access to patients with moderate fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis stage F2 or greater, or equivalent). There were no drug and alcohol use restrictions; however, several criteria (e.g., active injection drug use) were left to the discretion of the physician. Quebec did not reimburse simeprevir and sofosbuvir for people coinfected with HIV; no restrictions were found in the remaining jurisdictions. Prescriber type was restricted to specialists in up to 42% of provinces/territories. Interpretation This review of criteria of reimbursement of HCV direct-acting antivirals in Canada showed substantial interjurisdictional heterogeneity. The findings could inform health policy and support the development and adoption of a national HCV strategy.

Sulfamic acid is a potential material that exhibits excellent optical properties. A good quality, pure and dysprosium (Dy3+) doped (2.5 and 5 mol %) Sulfamic acid (SA) single crystals were grown successfully by slow cooling method. Structural study revealed a slight change in its lattice parameters and volume, suggesting the successful incorporation of Dy3+ in crystal system. The existence of dysprosium in the system was also confirmed. Presence of various vibrational modes was confirmed. Optical transparency was found to have a significant effect with variation in the doping concentration. Furthermore, a marked enhancement in its mechanical parameters with doping was also identified by nanoindentation technique. Etching study was also performed on the grown crystals to study the etch-pit formation and growth mechanism. Effect of doping on the thermal stability was analysed. All the results were compared and discussed in detail to get insight of the effect of doping concentration on Sulfamic acid crystal. (C) 2016 Elsevier B.V. All rights reserved.

Introduction Polymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN-λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN-λ3 plasma levels and the CC genotype. IFN-γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN-λ3 plasma levels did not correlate with function of NK cells and IFN-λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN-λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.

In present work, the pure and brilliant green dye doped single crystals of nonlinear optical zinc tris(thiourea) sulfate have been grown for the first time using slow evaporation solution technique from their aqueous solutions. The powder X-ray diffraction and FT-Raman spectroscopic investigations were carried out to confirm and identify the crystal structure and vibrational modes, respectively. The strong effect of dye on crystals morphology is observed. For optical band gap analysis the diffused reflectance was measured. Two absorption bands were observed in the diffused reflectance spectrum centered at ~425 and 627 nm due to brilliant green dye. Room temperature PL study with 310 nm excitation show noticeable enhancement in UV-blue emission band centered at 348 nm due to dye doping and also the enhancement in violet-blue emission centered at 420 nm was observed. Mechanical strength was also found to be enhanced with doping. All the results show that the properties of ZTS crystals are enriched due to dye doping and can be applied in optoelectronic devices.

This article presents a study on the influence of nano metakaolin (NMK) on physical, mechanical and microstructural properties of high volume vermiculite blended white Portland cement (WPC). WPC was replaced with 70 vol% expanded vermiculite (EVM), NMK were incorporated at a rate of 2, 4, 6, 8 and 10% as partial replacement by weight of EVM. The density, thermal conductivity, compressive strength, flexural strength, and capillary water absorption of the blended mixes were determined in accordance with ASTM standards at 28 days of curing. Differential scanning calorimeter (DSC) was used to study the phase transitions. The microstructure characteristics of the hardened samples were investigated by scanning electron microscope (SEM). The experimental results revealed a significant enhancement in both compressive and flexural strength, enhancements of about 57 and 59%, respectively were obtained at 10% NMK replacement. The capillary water absorption generally decreases with increasing replacements of EVM by NMK. A considerable decrease of about 74% was observed at 10% NMK. No significant effect of the NMK content on density and thermal conductivity. NMK led to noticeable improvement in the microstructure characteristics of the hardened blends.