Preparation, Characterization and Antibacterial Properties of Silver-Chitosan Nanocomposites Using Different Molecular Weight Grades of Chitosan

Purpose: To study the effect of chitosan molecular weight on the physicochemical and antibacterial properties of silver-chitosan nanoparticles.Methods: A series of silver-chitosan nanoparticles of different sizes were produced using various molecular weight (MW) grades of chitosan by an aqueous chemical reduction method. The nanoparticles were characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), scanningelectron microscopy (SEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and laser Doppler electrophoresis (LDE). The antibacterial properties of the nanoparticles were also evaluated by agar diffusion method.Results: The size of the silver-chitosan nanoparticles, ranging from 21.9 to 175.3 nm, was influenced by chitosan MW as well as by other process conditions. Although, the nanoparticles were not stable in liquid form, they however showed good stability in the solid state due to their low zeta potential. SEM images indicate that the nanoparticles were spherical. The antibacterial activity of the nanoparticles against Staphylococcus aureus increased with decrease in particle size owing to increase in surfacearea. The smallest particle size (21.9 nm) was obtained by using high chitosan MW at 4 °C and a stirring speed of 800 rpm.Conclusion: Chitosan is an effective agent for the preparation of silver nanoparticles. The size of the nanoparticles can be modulated by varying both chitosan MW and process conditions such as temperature and stirring speed

High-Gradient Magnetic Separator (HGMS) combined with adsorption for nitrate removal from aqueous solution

© 2018 Elsevier B.V. This paper investigates the adsorption of nitrate anions from aqueous solutions on ammonium-functionalized magnetic mesoporous silica. The adsorbent was prepared via two-step coating process of silica on magnetic core (Fe3O4). The resultant structure was modified by 3-aminopropyl triethoxysilane (APTES), and finally acidified in HCl solution to convert the grafted amino groups to ammonium ones. Field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), vibration sample magnetometer (VSM), Energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and N2 adsorption/desorption were used to characterize the obtained samples. Experimental results showed that several factors affected the uptake behavior such as pH, contact time, and initial concentration of nitrate. The amount of sorbent loading were examined and the adsorbent shows great adsorption capacity for NO3¯ (ca.51.28 mg g−1 at 25 °C). The nitrate loaded multifunctional microsphere can be easily regenerated with NaOH solution. The separation of multifunctional magnetic microspheres from solution by novel high gradient magnetic separation (HGMS), using the collection of rods, was also investigated in details. Contrast to other methods based on filter and batch conditions, large volumes of water can be easily handled by the new designed HGMS due to the decreasing pressure drop and retention times. The effect of a set of two different experimental variables, i.e. flowrate and magnetic field strength, were investigated to identify the best working conditions for the separation of adsorbent from treated water. The most efficient backwash system was offered to reuse the magnetic particles, too. The removal efficiency of NO3¯ from solution was around 86.24% by the constructed HGMS under the optimal experimental conditions of 7.5 mL s −1 flowrate and: 3.49 mT magnitude of the magnetic field

Assessing the Permeability of Engineered Capillary Networks in a 3D Culture

Many pathologies are characterized by poor blood vessel growth and reduced nutrient delivery to the surrounding tissue, introducing a need for tissue engineered blood vessels. Our lab has developed a 3D co-culture method to grow interconnected networks of pericyte-invested capillaries, which can anastamose with host vasculature following implantation to restore blood flow to ischemic tissues. However, if the engineered vessels contain endothelial cells (ECs) that are misaligned or contain wide junctional gaps, they may function improperly and behave more like the pathologic vessels that nourish tumors. The purpose of this study was to test the resistance to permeability of these networks in vitro, grown with different stromal cell types, as a metric of vessel functionality. A fluorescent dextran tracer was used to visualize transport across the endothelium and the pixel intensity was quantified using a customized MATLAB algorithm. In fibroblast-EC co-cultures, the dextran tracer easily penetrated through the vessel wall and permeability was high through the first 5 days of culture, indicative of vessel immaturity. Beyond day 5, dextran accumulated at the periphery of the vessel, with very little transported across the endothelium. Quantitatively, permeability dropped from initial levels of 61% to 39% after 7 days, and to 7% after 2 weeks. When ECs were co-cultured with bone marrow-derived mesenchymal stem cells (MSCs) or adipose-derived stem cells (AdSCs), much tighter control of permeability was achieved. Relative to the EC-fibroblast co-cultures, permeabilities were reduced 41% for the EC-MSC co-cultures and 50% for the EC-AdSC co-cultures after 3 days of culture. By day 14, these permeabilities decreased by 68% and 77% over the EC-fibroblast cultures. Co-cultures containing stem cells exhibit elevated VE-cadherin levels and more prominent EC-EC junctional complexes when compared to cultures containing fibroblasts. These data suggest the stromal cell identity influences the functionality and physiologic relevance of engineered capillary networks

PhD students, interculturality, reflexivity, community and internationalisation

Interviews with a small group of doctoral students at a British university indicate that the students feel that the programme provides an environment within which they develop interculturality through reflexive engagement with the PhD community and in some cases with the participants in their research. Significant here is that they are interpretivist, constructivist qualitative researchers within a larger university community of qualitative researchers where there is a shared reflexivity that is at the core of interculturality. They also bring with them existing cultural complexity with which to engage, build on, make reflexive sense of and resolve in this experience. This complexity which they all share make it difficult to consider them differently as 'international' or 'home' students, which are revealed as inappropriately divisive labels within an intercultural community. Where there are apparent issues with English as a second or other language among some of the students, it is realised that this represents a broader struggle, shared with all students, regarding self-expression in writing. These findings demand cultural belief in whatever backgrounds the students come from. This belief impacts on how we understand internationalisation and the nature of academic knowledge and process

Regional pressure and temperature differences across the injured human brain : comparisons between intraparenchymal and ventricular measurements

Introduction: Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The ‘gold standard’, based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neurominitoring. Methods: Patients with severe TBI requiring emergency surgery. Inclusion criteria: patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Results: Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n=8, craniotomy n=4) aged 21–78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature ‘pairs’ and 10,291 brain tissue-ventricular pressure ‘pairs’ were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p=0.92) or mean pressure readings (p=0.379) between tissue and ventricular sites. With 95.8% of paired temperature readings within 2SD (−0.4 to 0.4°C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5% of readings pairs fell within the 2SD range (−9.4756 to 7.8112 mmHg) (Fig. 2). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. Conclusions: There is good overall agreement between paired temperature measurements obtained from deep white matter and brain ventricle in patients with and without early neurosurgery. For paired ICP measurements, 93.5% of readings were within 2SD of mean difference. Whilst the majority of paired readings were comparable (within 10mmHg) clinically relevant tissue-ventricular dissociations were noted. Further work is required to unravel the events responsible for short intervals of pressure dissociation before tissue pressure readings can be definitively accepted as a reliable surrogate for ventricular pressure.</p

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based. METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations. RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management

TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

YesRecent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD) where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline rich motif. Here, we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2 hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.Faculty of Biological Sciences at the University of Leeds, Wellcome Trust Seed Award, Royal Society Research Grant RG150100, MR/K021303/1, Swedish Research Council (2014-3801) and the Medical Faculty at Lund University

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd