Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, and , respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Antibiotic sorption onto microplastics in water: A critical review of the factors, mechanisms and implications.

Microplastics as vectors for contaminants in the environment is becoming a topic of public interest. Microplastics have been found to actively adsorb heavy metals, per-fluorinated alkyl substances (PFAS), polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), pharmaceuticals and personal care products (PPCPs) and polybrominated diethers (PBDs) onto their surface. Particular interest in microplastics capacity to adsorb antibiotics needs further attention due to the potential role this interaction plays on antibiotic resistance. Antibiotic sorption experiments have been documented in the literature, but the data has not yet been critically reviewed. This review aims to comprehensively assess the factors that affect antibiotic sorption onto microplastics. It is recognised that the physico- chemical properties of the polymers, the antibiotic chemical properties, and the properties of the solution all play a crucial role in the antibiotic sorption capacity of microplastics. Weathering of microplastics was found to increase the antibiotic sorption capacity by up to 171%. An increase in solution salinity was found to decrease the sorption of antibiotics onto microplastics, in some instances by 100%. pH also has a substantial effect on sorption capacity, illustrating the significance of electrostatic interactions on the sorption of antibiotics onto microplastics. The need for a uniform experimental design when testing antibiotic sorption is highlighted to remove inconsistencies in the data currently presented. Current literature examines the link between antibiotic sorption and antibiotic resistance, however, further studies are still required to fully understand this emerging global crisis

Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

Evaluating the generation of microplastics from an unlikely source: The unintentional consequence of the current plastic recycling process.

This study casts light on the potential of microplastic generation during plastic recycling - an unintended consequence of the process. To date, microplastics have been detected in the wastewater and sludge from plastic recycling facilities; however, generation pathways, factors and minimisation strategies are understudied. The purpose of this study is to identify the factors affecting microplastic generation, namely, plastic type and weathering conditions. The size reduction phase, which involved the mechanical shredding of the plastic waste material, was identified to be the predominate source of microplastic generation. Material type was found to significantly affect microplastic generation rates. Focussing on the microplastic particles in the size range of 0.212-1.18 mm, polycarbonate (PC), polyethylene terephthalate (PET), polypropylene (PP), and high-density polyethylene (HDPE) generated 28,600 ± 3961, 21,093 ± 2211, 18,987 ± 752 and 6807 ± 393 particles/kg of plastic material shredded, respectively. The significant variations between different plastic types were correlated (R2 = 0.88) to the hardness of the plastic. Environmental weathering was observed to significantly affect microplastic generation rates. Generation rates increased for PC, PET, PP, and HDPE by 185.05 %, 159.80 %, 123.70 % and 121.74 %, respectively, over a six-month environmental exposure period. The results in this study confirm production of large amounts of microplastics from the plastic recycling industry through its operational processes, which may be a significant source for microplastic pollution if measures to reduce their production and removal from wastewater and sludge are not considered

Change in the chemical, mechanical and physical properties of plastics due to UVA degradation in different water matrices: A study on the recyclability of littered plastics.

To move towards a circular society, the recyclability potential of littered plastics should be explored to provide potential value for a product that is typically destined for landfill or incineration. This study aims to understand the changes in physical, mechanical, and chemical properties of four types of plastics (polyethylene terephthalate (PET), polypropylene (PP), polycarbonate (PC) and polylactic acid (PLA) after simulated environmental degradation. Plastic samples were subjected to different water matrices (in an attempt to simulate terrestrial, ocean, and river environments) to understand the role the environment plays on plastic degradation. Significant physical, mechanical, and chemical changes were observed for the PET, PP and PLA samples. Flakes and cracks were noted during the scanning electron microscopy (SEM) analysis of PET, PP and PLA illustrating the surface degradation that had occurred. Colour scanning of the samples provided complementary information about their suitability for upcycling or downcycling. Both PET and PP had visual colour changes, making them unsuitable for upcycling purposes. PLA had a significant decrease in its tensile strength in all environmental conditions, alongside significant chemical and surface change as revealed by Fourier-transform infrared (FTIR) and SEM analysis, respectively. PC had little to no changes in its chemical, mechanical, and physical properties due to high resistance to solar (UVA) degradation in presence of salt and natural organic matter in the form of humic acid. Therefore, out of the four types of plastics tested, PC was the only plastic determined to have good upcycling potential if collected from the environment. However, PET and PP could still be recycled into lower value products (i.e., construction materials)

Performance of a seawater-driven forward osmosis process for pre-concentrating digested sludge centrate: Organic enrichment and membrane fouling

© 2018 The Royal Society of Chemistry. This study demonstrated the potential of seawater-driven forward osmosis for enriching organic matter in digested sludge centrate. The results indicated that the cellulose triacetate membrane offered better performance than the polyamide membrane in terms of organic materials enrichment, fouling resistance and membrane cleaning efficiency. Membrane fouling decreased the enrichment efficiency of organic matter since the deposition of suspended particulate matter on the membrane surface caused fouling and loss of organic matter from the concentrated sludge centrate. The results showed that increasing the draw solution concentration increased flux but did not aggravate membrane fouling, however, it could reduce the efficiency of physical flushing to recover the flux. Seawater showed comparable forward osmosis performance to that of analytical grade NaCl as draw solutes in terms of flux and organic enrichment. The results also showed that seawater as the draw solution resulted in more membrane fouling and lower flux recovery compared to NaCl

Impact of bioplastic contamination on the mechanical recycling of conventional plastics.

Quality assurance of a recycled product is currently one of the biggest issues that the plastic recycling industry faces. The purity of the input plastic waste stream has significant influence over the quality of the recycled product. This research evaluated the impact of polylactic acid (PLA) contamination within the input waste stream of high-density polyethylene (HDPE) recycling. The ultimate tensile strength was noted to reduce by 50% when PLA contamination was at 10%. An investigation into the effect that UVA radiation (simulating solar radiation) has on HDPE contaminated with PLA was also performed to determine the long-term effect of the bioplastic contamination. After UVA treatment, the ultimate tensile strength was reported to reduce by 51% when PLA contamination was only at 2.5%. A water contact angle analysis indicated the PLA contamination increased the hydrophilic nature of the HDPE sheets, potentially creating issues if the intended use of the recycled product was to store liquids. Microscopic analysis of the HDPE sheets contaminated with PLA showed deformations, ridges, cracks, and holes appear on the surface due to the immiscibility of the two polymers that was confirmed by FTIR analysis. Colour changes were visibly noted, with UVA exposure increasing the rate of colour change. Based on the findings in this study, PLA contamination of even 1% in a HDPE waste stream would significantly reduce the quality of the recycled product

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the state of Qatar

Background: Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar. Methods: 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women’s Hospital and Primary Health Care Corporation in Doha, State of Qatar. HPV DNA detection was done using GP5+/6+ primers based real time-polymerase chain reaction (RT-PCR) assay followed by the usage of HPV type specific primers based RT- PCR reactions and Sanger sequencing for genotype identification. Results: Similar prevalence rates of HPV infection was identified in both Qatari and non-Qatari women at 6.2% and 5.9% respectively. HPV prevalence rate of 5.8% and 18.4% was identified in women with normal cytology and in women with abnormal cytology respectively. HPV 81, 11 and 16, in decreasing order were the most commonly identified genotypes. HPV 81 was the most frequent low-risk genotype among women with both normal (74.0%) and abnormal (33.3%) cytology. HPV 16 (4.6%) was identified as the predominant high-risk HPV genotype among women with normal cytology and HPV 16, HPV 18, and HPV 56 (22.2% each) were the most common identified high-risk genotypes in women with abnormal cytology Conclusions: The overall HPV prevalence in Arab women in Qatar was identified as 6.1% with an increased HPV prevalence seen in women with abnormal cytology results and no significant trends seen with age. In contrast to Western countries, we report a varied genotypic profile of HPV with a high prevalence of low-risk HPV genotype 81 among the Arab women residing in Qatar.Weill Cornell Medical College in Qatar; and by a grant from the Qatar National Research Fund (NPRP- 09-344-3-082)